Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo

Abstract Background Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo. Results We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone. Conclusion Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.

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Peanut-Shaped Gold Nanoparticles with Shells of Ceragenin CSA-131 Display the Ability to Inhibit Ovarian Cancer Growth In Vitro and in a Tumor Xenograft Model

Cancers ◽

10.3390/cancers13215424 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5424

Author(s):

Ewelina Piktel ◽

Ilona Oscilowska ◽

Łukasz Suprewicz ◽

Joanna Depciuch ◽

Natalia Marcińczyk ◽

...

Keyword(s):

Ovarian Cancer ◽

Gold Nanoparticles ◽

Xenograft Model ◽

Tumor Xenograft ◽

Assisted Delivery ◽

Anti Cancer ◽

Effective Inhibition ◽

Cancerous Cells

Gold nanoparticles-assisted delivery of antineoplastics into cancerous cells is presented as an effective approach for overcoming the limitations of systemic chemotherapy. Although ceragenins show great potential as anti-cancer agents, in some tumors, effective inhibition of cancer cells proliferation requires application of ceragenins at doses within their hemolytic range. For the purpose of toxicity/efficiency ratio control, peanut-shaped gold nanoparticles (AuP NPs) were functionalized with a shell of ceragenin CSA-131 and the cytotoxicity of AuP@CSA-131 against ovarian cancer SKOV-3 cells and were then analyzed. In vivo efficiency of intravenously and intratumorally administered CSA-131 and AuP@CSA-131 was examined using a xenograft ovarian cancer model. Serum parameters were estimated using ELISA methods. Comparative analysis revealed that AuP@CSA-131 exerted stronger anti-cancer effects than free ceragenin, which was determined by enhanced ability to induce caspase-dependent apoptosis and autophagy processes via reactive oxygen species (ROS)-mediated pathways. In an animal study, AuP@CSA-131 was characterized by delayed clearance and prolonged blood circulation when compared with free ceragenin, as well as enhanced anti-tumor efficiency, particularly when applied intratumorally. Administration of CSA-131 and AuP@CSA-131 prevented the inflammatory response associated with cancer development. These results present the possibility of employing non-spherical gold nanoparticles as an effective nanoplatform for the delivery of antineoplastics for the treatment of ovarian malignancy.

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hsa_circ_0003222 accelerates stemness and progression of non-small cell lung cancer by sponging miR-527

Cell Death and Disease ◽

10.1038/s41419-021-04095-8 ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Changhui Li ◽

Jiaqi Zhang ◽

Xiaohua Yang ◽

Cheng Hu ◽

Tianqing Chu ◽

...

Keyword(s):

Checkpoint Inhibitors ◽

Xenograft Model ◽

Therapy Resistance ◽

Circular Rna ◽

Cell Counting ◽

Tumor Xenograft ◽

Orthotopic Model ◽

Sphere Formation

AbstractThe relationship between circular RNA (circRNA) and cancer stem cells (CSCs) is uncertain. We have investigated the combined influence of CSCs, circRNA (hsa_circ_0003222), and immune checkpoint inhibitors in NSCLC progression and therapy resistance. We constructed lung CSCs (LCSCs; PC9 and A549). The effects of hsa_circ_0003222 in vitro were determined by cell counting, colony and sphere formation, and Transwell assays. A tumor xenograft model of metastasis and orthotopic model were built for in vivo analysis. We found that hsa_circ_0003222 was highly expressed in NSCLC tissues and LCSCs. Higher levels of hsa_circ_0003222 were associated with the stage, metastasis, and survival rate of patients with NSCLC. Reduced levels of hsa_circ_0003222 decreased tumor cell proliferation, migration, invasion, stemness-like properties, and chemoresistance. The silencing of hsa_circ_0003222 was found to downregulate PHF21B expression and its downstream, β-catenin by relieving the sponging effect of miR-527. Moreover, silencing hsa_circ_0003222 alleviated NSCLC resistance to anti-programmed cell death-ligand 1 (PD-L1)-based therapy in vivo. Our data demonstrate the significant role of hsa_circ_0003222 in NSCLC cell stemness-like properties. The manipulation of circRNAs in combination with anti-PD-L1 therapy may alleviate NSCLC stemness and progression.

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LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway

Cancer Cell International ◽

10.1186/s12935-021-01808-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bo Jia ◽

Junfeng Dao ◽

Jiusong Han ◽

Zhijie Huang ◽

Xiang Sun ◽

...

Keyword(s):

Noncoding Rna ◽

Xenograft Model ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Cell Cycle Regulators ◽

Normal Tissues ◽

Stat3 Signaling ◽

Long Intergenic Noncoding Rna

Abstract Background Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. Methods The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2′-deoxyuridline (EdU) assay and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. Results LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo. In mechanism, LINC00958 acted as a ceRNA by competitively sponging miR-211-5p. In addition, we identified CENPK as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Furthermore, The overexpression of CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. Conclusions Our findings suggested that LINC00958 is a potential prognostic biomarker in TSCC.

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Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis

Scientific Reports ◽

10.1038/s41598-020-80911-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kazim Husain ◽

Domenico Coppola ◽

Chung S. Yang ◽

Mokenge P. Malafa

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Metastasis ◽

Annexin V ◽

Cancer Cell Growth ◽

Ki 67 ◽

Sox2 Expression ◽

Tumour Metastasis

AbstractThe activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have shown that farnesyl dimethyl chromanol (FDMC) inhibits cancer cell growth and induces apoptosis in vitro and in vivo. We provide the first demonstration that FDMC inhibits CCSC viability, survival, self-renewal (spheroid formation), pluripotent transcription factors (Nanog, Oct4, and Sox2) expression, organoids formation, and Wnt/β-catenin signalling, as evidenced by comparisons with vehicle-treated controls. In addition, FDMC inhibits CCSC migration, invasion, inflammation (NF-kB), angiogenesis (vascular endothelial growth factor, VEGF), and metastasis (MMP9), which are critical tumour metastasis processes. Moreover, FDMC induced apoptosis (TUNEL, Annexin V, cleaved caspase 3, and cleaved PARP) in CCSCs and CCSC-derived spheroids and organoids. Finally, in an orthotopic (cecum-injected CCSCs) xenograft metastasis model, we show that FDMC significantly retards CCSC-derived tumour growth (Ki-67); inhibits inflammation (NF-kB), angiogenesis (VEGF and CD31), and β-catenin signalling; and induces apoptosis (cleaved PARP) in tumour tissues and inhibits liver metastasis. In summary, our results demonstrate that FDMC inhibits the CCSC metastatic phenotype and thereby supports investigating its ability to prevent CRC metastases.

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Anti‐oral cancer effects of triptolide by downregulation of DcR3 in vitro, in vivo, and in preclinical patient‐derived tumor xenograft model

Head & Neck ◽

10.1002/hed.25554 ◽

2018 ◽

Vol 41 (5) ◽

pp. 1260-1269 ◽

Cited By ~ 1

Author(s):

Cheng‐Yu Yang ◽

Chih‐Kung Lin ◽

Cheng‐Chih Hsieh ◽

Chang‐Huei Tsao ◽

Chun‐Shu Lin ◽

...

Keyword(s):

Oral Cancer ◽

Xenograft Model ◽

Tumor Xenograft

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LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway

10.21203/rs.3.rs-78207/v2 ◽

2021 ◽

Author(s):

Bo Jia ◽

Junfeng Dao ◽

Jiusong Han ◽

Zhijie Huang ◽

Xiang Sun ◽

...

Keyword(s):

Noncoding Rna ◽

Xenograft Model ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Cell Cycle Regulators ◽

Normal Tissues ◽

Stat3 Signaling ◽

Long Intergenic Noncoding Rna

Abstract Background: Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. Methods: The expression levels of LINC00958 in human TSCC tissues and adjacent normal tissues were detected. The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2’-deoxyuridline (EdU) assay, and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. Results: We found LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo . In mechanism, LINC00958 acted as a competing endogenous RNA (ceRNA) by competitively sponging miR-211-5p. In addition, we identified centromere protein K (CENPK) as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Conclusion: Furthermore, CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. Our findings suggest that LINC00958 is a potential prognostic biomarker in TSCC.

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Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01743-3 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Chongyang Li ◽

Chaowei Deng ◽

Guangzhao Pan ◽

Xue Wang ◽

Kui Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Xenograft Model ◽

Resistant Cell ◽

Tumor Xenograft ◽

Gastric Cancer Cells ◽

Bcl2 Family ◽

Ubiquitin E3 Ligase ◽

Underlying Mechanisms

Abstract Background Lycorine hydrochloride (LH), an alkaloid extracted from the bulb of the Lycoris radiata, is considered to have anti-viral, anti-malarial, and anti-tumorous effects. At present, the underlying mechanisms of LH in gastric cancer remain unclear. MCL1, an anti-apoptotic protein of BCL2 family, is closely related to drug resistance of tumor. Therefore, MCL1 is considered as a potential target for cancer treatment. Methods The effect of LH on gastric cancer was assessed in vitro (by MTT, BrdU, western blotting…) and in vivo (by immunohistochemistry). Results In this study, we showed that LH has an anti-tumorous effect by down-regulating MCL1 in gastric cancer. Besides, we unveiled that LH reduced the protein stability of MCL1 by up-regulating ubiquitin E3 ligase FBXW7, arrested cell cycle at S phase and triggered apoptosis of gastric cancer cells. Meanwhile, we also demonstrated that LH could induce apoptosis of the BCL2-drug-resistant-cell-lines. Moreover, PDX (Patient-Derived tumor xenograft) model experiment proved that LH combined with HA14–1 (inhibitor of BCL2), had a more significant therapeutic effect on gastric cancer. Conclusions The efficacy showed in our data suggests that lycorine hydrochloride is a promising anti-tumor compound for gastric cancer.

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Garcinol-loaded novel cationic nanoliposomes: in vitro and in vivo study against B16F10 melanoma tumor model

Nanomedicine ◽

10.2217/nnm-2019-0022 ◽

2019 ◽

Vol 14 (15) ◽

pp. 2045-2065 ◽

Cited By ~ 1

Author(s):

Brahamacharry Paul ◽

Raghuvir H Gaonkar ◽

Ria Mukhopadhyay ◽

Shantanu Ganguly ◽

Mita Chatterjee Debnath ◽

...

Keyword(s):

Chromatin Condensation ◽

Xenograft Model ◽

Tumor Model ◽

Tumor Xenograft ◽

B16f10 Melanoma ◽

Melanoma Tumor ◽

Study Gene Expression ◽

The Difference

Aim: Garcinol (GAR)-loaded cationic nanoliposomes were developed to achieve potential antitumor efficacy on B16F10 melanoma cells in vitro and in vivo. Materials & methods: Two different phospholipids namely, distearoyl phosphatidylcholine (DSPC) and dipalmitoyl phosphatidylcholine (DPPC) were used in formulation to elucidate the difference in cellular uptake, cytotoxicity, in vivo tumor uptake (by scintigraphic imaging after technetium-99m radiolabeling) and therapeutic efficacy. Results: Different in vitro protocols, for example, MTT assay, apoptosis study, gene expression analysis, chromatin condensation and cytoskeleton breakdown analysis in B16F10 cell lines as well as scintigraphic analysis and tumor inhibition studies (B16F10 tumor xenograft model) revealed superiority of GAR-DPPC than GAR-DSPC and free GAR in melanoma prevention. Conclusion: Cationic nanoliposomal formulations could be a future medication for skin cancer treatment.

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Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Cancers ◽

10.3390/cancers12030672 ◽

2020 ◽

Vol 12 (3) ◽

pp. 672 ◽

Cited By ~ 5

Author(s):

Roberta Affatato ◽

Laura Carrassa ◽

Rosaria Chilà ◽

Monica Lupi ◽

Valentina Restelli ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

High Throughput Screening ◽

Therapeutic Option ◽

Xenograft Model ◽

Antimitotic Drugs ◽

M Phase ◽

Sirna Library

Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC.

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