Study on Extraction Process of Root of Henry Wood Betony Polysaccharides and Their Antitumor Activity against S180

We optimized the hot water extraction of polysaccharides from the root of Henry wood betony (RHWPs) using a uniform test and explored their anti-tumor activities in vitro and in vivo. The optimal extraction conditions were as follows: 40 min extraction time, liquid/solid ratio 30 mL/g, 100 min soaking time, two extraction cycles, 100% ethanol concentration, and extraction temperature of 80 °C. The molecular weight distribution of RHWPs with MWs was 228,600 g/mol and 5001 g/mol. The IR spectrum further indicated that RHWPs are acidic polysaccharides containing pyranose and furan rings. The main monosaccharides found in RHWPs were mannose, ribose, l-rhamnose monohydrate, glucuronic acid, galacturonic acid, glucose, galactose, xylose, arabinose, and fucose. RHWPs inhibited the proliferation of S180 tumor cells and induced apoptosis in vitro. Oral administration of RHWPs to tumor-bearing mice significantly inhibited the growth of the S180 xenografts, accelerated apoptosis in tumor cells, and expanded the necrotic regions. Furthermore, RHWPs also markedly increased the levels of TNF-α, IFN-γ, and IL-2 in the sera of tumor-bearing mice, and activated immune cells such as lymphocytes, NK cells, and macrophages, thereby inducing tumor cell apoptosis. Taken together, RHWPs are a promising anti-tumor agent that ought to be explored further.

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In Situ Silver-based Electrochemical Bioreactor In Vivo

10.21203/rs.3.rs-103588/v1 ◽

2020 ◽

Author(s):

Yong Huang ◽

Liping Zhong ◽

Zhiming Deng ◽

Pan Wu ◽

Jian He ◽

...

Keyword(s):

Silver Nanoparticles ◽

Graphene Oxide ◽

Tumor Cells ◽

Silver Nanoparticle ◽

A549 Cells ◽

Induced Apoptosis ◽

Induced Changes

Abstract In this study we show for the first time that a reduced graphene oxide (rGO) carrier has a 15-fold higher catalysis rate than graphene oxide (GO) in Ag+ reduction. Based on this, we constructed a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which unlocked an Ag+ prodrug to generate silver nanoparticles and inhibited the growth of various tumors. In this bioreactor system, intratumoral H2O2 acted as the reductant and the rGO carrier acted as the catalyst. Chelation of aptamers to this prodrug increased the production of silver nanoparticles by tumor cells, especially in the presence of Vitamin C, which broke down in tumor cells to supply massive amounts of H2O2. Consequently, highly efficient silver nanoparticle-induced apoptosis was observed in HepG2 and A549 cells in vitro and in HepG2- and A549-derived tumors in vivo. The apoptosis was associated with ROS-induced changes in mitochondrial membrane potential and DNA damage. The specific aptamer targeting and intratumoral silver nanoparticle production guaranteed excellent biosafety, with no damage to normal cells, because the Ag+ prodrug was specifically unlocked in tumors. More significantly, there was no evident tissue damage in monkeys, which greatly increases the clinical translation potential of the SEOB system.

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Osteopontin Blockade Immunotherapy Increases Cytotoxic T Lymphocyte Lytic Activity and Suppresses Colon Tumor Progression

Cancers ◽

10.3390/cancers13051006 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1006

Author(s):

John D. Klement ◽

Dakota B. Poschel ◽

Chunwan Lu ◽

Alyssa D. Merting ◽

Dafeng Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Growth ◽

Tumor Cells ◽

T Cell Activation ◽

Cell Activation ◽

Lymphoid Cells ◽

Colon Tumor ◽

Tumor Bearing

Human colorectal cancers are mostly microsatellite-stable with no response to anti-PD-1 blockade immunotherapy, necessitating the development of a new immunotherapy. Osteopontin (OPN) is elevated in human colorectal cancer and may function as an immune checkpoint. We aimed at elucidating the mechanism of action of OPN and determining the efficacy of OPN blockade immunotherapy in suppression of colon cancer. We report here that OPN is primarily expressed in tumor cells, myeloid cells, and innate lymphoid cells in human colorectal carcinoma. Spp1 knock out mice exhibit a high incidence and fast growth rate of carcinogen-induced tumors. Knocking out Spp1 in colon tumor cells increased tumor-specific CTL cytotoxicity in vitro and resulted in decreased tumor growth in vivo. The OPN protein level is elevated in the peripheral blood of tumor-bearing mice. We developed four OPN neutralization monoclonal antibodies based on their efficacy in blocking OPN inhibition of T cell activation. OPN clones 100D3 and 103D6 increased the efficacy of tumor-specific CTLs in killing colon tumor cells in vitro and suppressed colon tumor growth in tumor-bearing mice in vivo. Our data indicate that OPN blockade immunotherapy with 100D3 and 103D6 has great potential to be further developed for colorectal cancer immunotherapy and for rendering a colorectal cancer response to anti-PD-1 immunotherapy.

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Glucocorticoids impair oocyte competence and trigger apoptosis of ovarian cells via activating the TNF-α system

Reproduction ◽

10.1530/rep-20-0025 ◽

2020 ◽

Vol 160 (1) ◽

pp. 129-140 ◽

Cited By ~ 1

Author(s):

Hong-Jie Yuan ◽

Zhi-Bin Li ◽

Xin-Yue Zhao ◽

Guang-Yi Sun ◽

Guo-Liang Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Types ◽

Developmental Potential ◽

Oocyte Competence ◽

Ovarian Cells ◽

Tnf Α ◽

Induced Apoptosis ◽

Apoptotic Effects

Mechanisms by which female stress and particularly glucocorticoids impair oocyte competence are largely unclear. Although one study demonstrated that glucocorticoids triggered apoptosis in ovarian cells and oocytes by activating the FasL/Fas system, other studies suggested that they might induce apoptosis through activating other signaling pathways as well. In this study, both in vivo and in vitro experiments were conducted to test the hypothesis that glucocorticoids might trigger apoptosis in oocytes and ovarian cells through activating the TNF-α system. The results showed that cortisol injection of female mice (1.) impaired oocyte developmental potential and mitochondrial membrane potential with increased oxidative stress; (2.) induced apoptosis in mural granulosa cells (MGCs) with increased oxidative stress in the ovary; and (3.) activated the TNF-α system in both ovaries and oocytes. Culture with corticosterone induced apoptosis and activated the TNF-α system in MGCs. Knockdown or knockout of TNF-α significantly ameliorated the pro-apoptotic effects of glucocorticoids on oocytes and MGCs. However, culture with corticosterone downregulated TNF-α expression significantly in oviductal epithelial cells. Together, the results demonstrated that glucocorticoids impaired oocyte competence and triggered apoptosis in ovarian cells through activating the TNF-α system and that the effect of glucocorticoids on TNF-α expression might vary between cell types.

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Wogonin sensitizes resistant malignant cells to TNFα- and TRAIL-induced apoptosis

Blood ◽

10.1182/blood-2006-03-011973 ◽

2006 ◽

Vol 108 (12) ◽

pp. 3700-3706 ◽

Cited By ~ 79

Author(s):

Stefanie C. Fas ◽

Sven Baumann ◽

Jia Yun Zhu ◽

Marco Giaisi ◽

Monika K. Treiber ◽

...

Keyword(s):

Side Effects ◽

Tumor Cells ◽

Chinese Herb ◽

Protein Synthesis Inhibitors ◽

Normal Peripheral Blood ◽

Herbal Compound ◽

Induced Apoptosis ◽

Potential Use

AbstractTNFα has previously been used in anticancer therapy. However, the therapeutic application of TNFα was largely limited due to its general toxicity and the fact that it activates the NF-κB–family transcription factors, which are proinflammatory and antiapoptotic. To overcome this problem in vitro, specific NF-κB inhibitors or transcription or protein synthesis inhibitors such as actinomycin D and cycloheximide are usually used in combination to increase TNFα killing of tumor cells. However, these agents also cause harmful side effects in vivo. We show here that wogonin, derived from the popular Chinese herb Huang-Qin, attenuates NF-κB activity by shifting TNFα-induced free radical ·O2– to a more reduced nonradical product, H2O2, and thereby sensitizes TNFα-resistant leukemia cells to TNFα-induced apoptosis. Importantly, wogonin does not affect the viability of normal peripheral blood T cells. Wogonin also sensitizes TRAIL-induced apoptosis. Our data suggest a potential use of wogonin as a TNFα or TRAIL adjuvant for cancer treatment. Our data also demonstrate how a herbal compound enhances killing of tumor cells with reduced side effects compared with other treatments.

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Bortezomib Is Synergistic with Rituximab and Cyclophosphamide in Inducing Apoptosis of Mantle Cell Lymphoma Cells In Vitro and In Vivo.

Blood ◽

10.1182/blood.v110.11.4514.4514 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4514-4514

Author(s):

Liang Zhang ◽

Yuankai Shi ◽

Xiaohong Han ◽

Jing Yang ◽

Jianfei Qian ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Tumor Cells ◽

Cell Lines ◽

Primary Tumor ◽

Cell Lymphoma ◽

Fixed Dose ◽

Mantle Cell ◽

Induced Apoptosis

Abstract Introduction: Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome. Although frontline therapy induces a high rate of complete remission, relapse is inevitable and new regimens are needed for relapsed MCL. The proteasome inhibitor bortezomib (BTZ) induces apoptosis and sensitizes MCL cells to chemotherapy in relapsed MCL, but as a single agent, response rate is low, duration of response is short and side effects are severe. Here we evaluated whether BTZ is additive or synergistic with cyclophosphamide (CTX) and rituximab (RTX). Material and Methods: Four human MCL cell lines SP53, MINO, Grant 519, and Jeko-1 and freshly isolated primary tumor cells from three MCL patients were treated with BTZ, CTX, RTX individually or in combination of RTX and CTX (RC), or BTZ plus RTX and CTX (BRC regimen). Cell proliferation and apoptosis were evaluated to determine if there was additive or synergistic effect of the BRC regimen. Western blot analysis was used to elucidate the molecular mechanism by which BTZ, RTX, CTX, RC and BRC induces apoptosis in MCL cells. In addition, in vivo experiments using severe combined immunodeficiency mice with human mantle cell lymphoma xenografts were performed to examine the in vivo efficacy of the regimen to control the growth of and eradicate MCL cells. Results: BTZ and CTX as single agents inhibited the growth of MCL cell lines in a dose-dependent manner (P < 0.01). The IC50 (inhibitory concentration at 50%) for BTZ and for CTX were between 10 and 20 nM and between 5 and 20 mM, respectively. Increasing doses of BTZ with a fixed dose of RTX (10 μg/mL) and CTX (10 mM) resulted in markedly synergistic growth inhibition of MCL cells (P < 0.01). The BRC regimen induced apoptosis in about 69.7% of MCL cell lines and 92.6% of primary tumor cells (P < 0.05 and P < 0.01, compared with those induced by BTZ, RTX, CTX or RC). Furthermore, western blotting analysis showed that BRC induced apoptosis earlier via activation and cleavage of caspases-8, -9, and -3, and PARP as compared with BTZ, RTX, CTX or RC. The pan-caspase inhibitor z-VAD-FMK completely blocked apoptosis induced by BRC. In vivo studies demonstrated that BRC regimen eradicated subcutaneous tumors in MCL-bearing SCID mice and significantly prolonged the long-term event-free survival up to 10 weeks in 70% of the mice, whereas all tumor-bearing mice receiving BTZ, RTX, CTX or RC or PBS (control) died of aggressive MCL within 6 weeks. Conclusion: Cytoreductive chemotherapy with both BTZ and anti-CD20 antibody effectively inhibited the growth and induced apoptosis of MCL cells in vitro and in vivo. Bortezomib-rituximab-cyclophosphamide (BRC) regimen may offer a better therapeutic modality for MCL patients. Thus, our data lay the basis for a clinical trial in relapsed MCL using the BRC combination treatment.

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Darbepoetin alfa Radiosensitizes Tumors Independent of Anemia or the Correction of Anemia.

Blood ◽

10.1182/blood.v104.11.1637.1637 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1637-1637

Author(s):

Shoucheng Ning ◽

Sinclair Angus ◽

Hartley Cynthia ◽

Knox Susan4

Keyword(s):

Tumor Growth ◽

Tumor Cells ◽

Fold Increase ◽

Growth Delay ◽

Local Tumor ◽

Tumor Growth Delay ◽

Tumor Bearing ◽

Tumor Irradiation

Abstract Darbepoetin alfa (DA) is a FDA approved long acting erythropoietic protein. We hypothesized that correction of anemia in tumor-bearing mice by DA would secondarily increase the tumor pO2 and potentiate radiation-induced cell killing of tumor cells. To test this hypothesis, we used total body irradiation (TBI) to induce anemia in C3H mice. Murine squamous cell carcinoma tumor (SCC VII) and fibrosarcoma (RIF-1) models were used to study tumor responses to radiation in vivo. DA (30μg/kg) was administered i.p. either every two weeks or weekly. EPO-R RNA levels were measured in tumors from normal, anemic and DA treated mice in both tumor models. Tumors were locally irradiated with daily fractions of 250 cGy for 5 days. Following 500 cGy TBI, hemoglobin levels decreased and reached a nadir of 7.0 ± 0.9 gm/dL 14 days post TBI. Administration of DA reduced the depth and duration of anemia and improved the general health condition of anemic animals as evidenced by accelerated recovery of body weight following the TBI and maintenance of normal levels of activity compared to similarly irradiated animals not treated with DA. Mice treated with DA on the same day as the TBI had elevated hemoglobin levels with a nadir of 11.1 gm/dL on day 14 after TBI. Systemic administration of DA alone did not stimulate tumor growth in TBI-induced anemic mice. When combined with fractionated local tumor irradiation, administration of DA at any of the time points studied (18, 11, 4 and 0 days before initiation of local tumor irradiation) delayed tumor growth and increased the tumor growth delay time from 2.7 days for irradiation alone to 7.3 – 10.6 days for DA treated animals (p < 0.01). There was no statistically significant difference between tumor growth delay times for groups of mice treated with DA at various times before tumor irradiation. Although DA effectively corrected anemia in tumor-bearing mice and significantly decreased the number of hypoxic cells in the tumors as shown by EF5 staining, radiosensitization by DA was independent of the correction of anemia. EPOR RNA expression was barely detectible in tumors cultured in vitro. There were no differences in EPO-R RNA levels in tumors from anemic or DA treated mice (1–2 fold increase), although EPO-R transcription was upregulated in tumors grown in vivo compared to control tumors lines grown in vitro (40–80 fold increase). This may be due to hypoxic induction of EPO-R by tumors in vivo or expression of EPO-R by endothelial cells or infiltrating macrophages. Results from an experiment in non-anemic mice with RIF-1 tumors suggest that DA can sensitize tumor cells in non-anemic mice to radiation as well. These results support the idea that radiosensitization by DA is independent of hemoglobin and tumor pO2. It has long been assumed that anemia causes decreased tumor oxygenation and increased tumor radioresistance, and that correction of anemia would therefore increase tumor pO2, and result in enhanced radiosensitivity. However, the data presented here challenge this presumed relationship. These findings are promising and may have relevance to the treatment of patients with a variety of tumor types with radiation therapy.

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The Human Anti-CD30 Antibody 5F11 Activates NF-kB and Sensitizes Lymphoma Cells to Bortezomib Induced Apoptosis.

Blood ◽

10.1182/blood.v104.11.3295.3295 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3295-3295 ◽

Cited By ~ 2

Author(s):

Elke Pogge ◽

Boris Boell ◽

Samir Tawadros ◽

Katrin Reiners ◽

Peter Borchmann ◽

...

Keyword(s):

Tumor Cells ◽

Cell Lines ◽

Human Monoclonal Antibody ◽

Cell Nuclei ◽

Lymphoma Cells ◽

Initial Activation ◽

Induced Apoptosis ◽

Hodgkin Cell

Abstract Purpose: We recently developed a fully human monoclonal antibody (5F11) directed against the CD30 receptor, which is an excellent target for antibody based immunotherapy of malignant lymphoma cells. The antibody is cytotoxic for lymphoma cells in vitro and in vivo, however a partial or even complete resistance of several Hodgkin cell lines has been observed. In this study we analysed, whether the efficacy of 5F11 can be improved by combination with bortezomib. Methods and Results: Bortezomib is an inhibitor of the ubiquitin-proteasomes pathway that is toxic to multiple solid and hemotologic tumor cells. Using XTT viability assays, TUNEL assays and Facs analysis we demonstrate a synergistic toxic effect of 5F11 and bortezomib on the Hodgkin cell lines tested (L540, L1236, L428) and the CD30 expressing ALCL Karpas299. Moreover the growth of subcutaneous L540 derived tumors in SCID mice is inhibited by 5F11 in combination with bortezomib. The synergy depends on the regime of the drugs and is only seen when a pre-incubation with the antibody is followed by exposure to bortezomib. Immunofluorescence analysis demonstrates that the sensitization of the tumor cells correlates with a 5F11 dependent localisation of the survival factor NF-kB into the cell nuclei. A transfected NF-kB responsive reporter gene is 2–3 fold activated in 5F11 treated L428 cells and enhanced NF-kB binding is detected performing EMSA.. We furthermore measured an increased expression of the NF-kB target gene c-flip, that is down regulated after additional incubation of the tumor cells with bortezomib. Conclusion: Our data indicate that initial activation of NF-kB and downstream anti-apoptotic proteins in response to 5F11 via CD30 sensitizes the tumor cells to bortezomib induced cell death. The in vitro and in vivo activity of the combination of 5F11 and bortezomib suggests a therapeutic value for the treatment of HD patients.

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Osteoclasts in Myeloma Are Derived from Gr-1+CD11b+ Myeloid Immune Suppressor Cells of the Bone Marrow Niche in Vivo

Blood ◽

10.1182/blood.v112.11.736.736 ◽

2008 ◽

Vol 112 (11) ◽

pp. 736-736 ◽

Cited By ~ 1

Author(s):

Junling Zhuang ◽

Li Yang ◽

Seint T Lwin ◽

Claire M. Edwards ◽

James R Edwards ◽

...

Keyword(s):

Bone Marrow ◽

Tumor Cells ◽

Suppressor Cells ◽

Bone Lesions ◽

Vicious Cycle ◽

Tumor Bearing ◽

Immune Suppressor Cells ◽

Immune Suppressor

Abstract When cancer cells are resident in bone, they initiate a vicious cycle with osteoclasts (OCs) which perpetuates their growth and aggressive behavior. OCs are critical for the maintenance of the vicious cycle, since they control not only bone destruction associated with cancer, but also the aggressive behavior of tumor cells. It has recently been recognized that tumor cells grow in distant sites because they induce non-malignant cells to establish a “pre-metastatic niche” for tumor cells to later engraft. But nothing is yet known for bone. Primitive bone marrow progenitor cells, called myeloid immune suppressor cells (MISCs), which suppress immune reactivity, are important niche components. MISCs belong to the myelomonocytic lineage with surface markers of Gr-1 and CD11b. We hypothesize that MISCs are precursors of OCs recruited by tumors to assist in the establishment of the vicious cycle. To test this hypothesis, we used the well-characterized 5TGM1 murine myeloma model. 5TGM1-GFP tagged myeloma cells were inoculated via tail vein. The proportion of Gr-1+CD11b+ cells in bone marrow and spleen were assessed by FACS. On week 4 after tumor cell inoculation, %Gr-1+CD11b+ cells were significantly greater in tumor-bearing mice compared with controls (60.9±7.8% vs 37.7±8.6% p<0.05 in marrow; 21.1±4.84% vs 2.4±0.85% p<0.05 in spleen) and paralleled the myeloma burden in bone and spleen. We sorted the Gr-1+CD11b+ cells from the spleens by using magnetic microbeads. MISCs formed multinucleated TRAP positive OCs in medium containing M-CSF (25ng/ml) and RANKL (50ng/ml). The number of OCs derived from tumor MISCs was dramatically greater than those from control mice after 14 day culture (13.4±2.1 vs 1±0.7 per 100x field). MISCs expressed the αv chain of the vitronectin receptor (CD51) and the calcitonin receptor which are specific markers for OCs as they differentiated into multinucleated TRAP+ cells. Only MISCs from tumor-bearing mice and not MISCs from control mice caused resorption pits on dentine discs, demonstrating they were functional OCs. To study the in vivo differentiation of MISCs, we bred lacZ generalized C57 B6 mice with Rag2−/− immune compromised mice to generate lacZ+/− Rag2−/− mice. MISCs were sorted from lacZ+/− Rag2−/− myeloma mice. lacZ positive MISCs were co-injected with 5TGM1 cells to Rag2−/− mice. On day 10 after injection, lacZ+ multinucleated cells could be seen on endosteal surface beneath growth plate by X-gal staining. Those lacZ+ cells were also TRAP+, indicating they were OCs. Treatment of mice with zoledronic acid 100ug/kg s.c. 2/week for 4 weeks reduced % MISCs in tumor bearing mice and impaired the capacity of MISCs to form OCs in vitro (OC# 42.4±4.0 vs 25.6±3.5 per 100x field). Our data suggest that MISCs are increased significantly in marrow and spleen of myeloma-bearing mice and parallel the appearance of lytic bone lesions. These MISCs differentiate avidly and rapidly into functional OCs in vitro as well as in vivo. Zoledronic acid impairs both MISCs, the OC precursors, and mature OCs. These results have a number of implications, including the possibility of reducing bone lesions in myeloma and other malignancies by depleting specific subpopulations of osteoclast precursors.

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MODL-22. DEVELOPING A REAL-TIME PERSONALIZED DRUG TESTING PLATFORM FOR PEDIATRIC CNS CANCERS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.595 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii415-iii415

Author(s):

Sandra Laternser ◽

Chiara Cianciolo Cosentino ◽

Justyna M Przystal ◽

Susanne Dettwiler ◽

Elisabeth Jane Rushing ◽

...

Keyword(s):

Real Time ◽

Tumor Cells ◽

Drug Testing ◽

Combination Drug ◽

Sequencing Platform ◽

Tumor Bearing ◽

Screening Platform ◽

Effective Drugs

Abstract INTRODUCTION The relatively small size of biopsied CNS tumors has presented a historical challenge for real-time drug screens. Moreover, in vivo assessment of drug response does not often benefit patients with aggressive gliomas given the relatively long time (>8 months) of tumor engraftment in the classic mouse PDX models. Here, we aimed to develop an innovative real-time in vivo and in vitro drug screening platform capable of analyzing a minimal number (<1E6) of cells obtained at biopsy. METHODS Existing primary cells were used to test 6 different culture platforms. The top platform was selected and used to expand tumor cells obtained of DMG biopsy. Tumor cells were validated using the minION sequencing platform. Single and combination drug (n=7) screens were performed. Effective drugs were further evaluated in zebrafish PDX and non-tumor bearing models to assess efficacy and toxicity, respectively. RESULTS A total of 8 biopsies were obtained. Successful cell expansion was achieved in 6/8 (75%) and a limited drug screen in 3/6 (50%) of cases. Single and combination drug (n=7) assays identified responder and non-responders to candidate drugs. Systemic toxicity of effective drugs was tested in non-tumor bearing zebrafish. Tumor cells were engrafted in zebrafish providing the opportunity for an in vivo screen. The entire process was completed within 21 days on average. CONCLUSIONS A novel platform was developed for rapid in vitro and in vivo drug screens of tumor cells obtained at biopsy. This platform will provide the opportunity to establish personalized therapy for heterogeneous cancers including DMGs.

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GliPR1 knockdown by RNA interference exerts anti‐glioma effects in vitro and in vivo

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03737-3 ◽

2021 ◽

Author(s):

Urban J. Scheuring ◽

Steffi Ritter ◽

Daniel Martin ◽

Gabriele Schackert ◽

Achim Temme ◽

...

Keyword(s):

Rna Interference ◽

Nude Mice ◽

Cellular Proliferation ◽

Glioma Cells ◽

Clonogenic Survival ◽

Tumor Bearing ◽

Shrna Vector ◽

Induced Apoptosis

Abstract Introduction In human glioblastomas, glioma pathogenesis-related protein1 (GliPR1) is overexpressed and appears to be an oncoprotein. We investigated whether GliPR1 knockdown in glioma cells by RNA interference exerts anti-glioma effects. Methods Experiments used human glioblastoma cell lines transduced with GliPR1 shRNA (sh#301, sh#258). Transduction produced stringent doxycycline-dependent GliPR1 knockdown in clones (via lentiviral “all-in-one” TetOn-shRNA vector) or stable GliPR1 knockdown in polyclonal cells (via constitutive retroviral-shRNA vector). In vitro assessments included cellular proliferation and clonogenic survival. In vivo assessments in tumor-bearing nude mice included tumor growth and survival. Results Using doxycycline-dependent GliPR1 knockdown, shGliPR1-transduced U87-MG clones demonstrated reductions in cellular proliferation in the presence versus absence of doxycycline. Using stable GliPR1 knockdown, polyclonal shGliPR1-transduced U87-MG, A172, and U343-MG cells consistently showed decreased clonogenic survival and induced apoptosis (higher proportion of early apoptotic cells) compared to control shLuc-transduced cells. In tumor-bearing nude mice, using doxycycline-dependent GliPR1 knockdown, subcutaneous and cranial transplantation of the U87-MG clone 980-5 (transduced with GliPR1 sh#301) resulted in reduced subcutaneous tumor volume and cerebral tumor area in doxycycline-treated mice versus those left untreated. Using stable GliPR1 knockdown, nude mice cranially transplanted with polyclonal U87-MG cells transduced with GliPR1 sh#258 had significantly prolonged survival compared to mice cranially transplanted with control shLuc-transduced cells (41 versus 26 days; P < 0.001). Conclusion GliPR1 knockdown in glioma cells decreased cellular proliferation, decreased clonogenic survival, and induced apoptosis in vitro, and reduced glioblastoma tumor growth and prolonged survival in vivo. These findings support that GliPR1 may have potential value as a therapeutic target.

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