scholarly journals Therapeutic effect of YSY01 on osteoarthritis in rabbit: involvement of suppressing signaling pathway of NF-kB and MMP-9

2021 ◽  
Author(s):  
Zhou Yang ◽  
Feng Zhan ◽  
Shu-dian Lin ◽  
Ying Liu ◽  
Yu-wei Zhan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Viability ◽  
Therapeutic Effect ◽  
Inhibitory Effect ◽  
Flow Cytometry Analysis ◽  
Cellular Models ◽  
Positive Therapeutic Effect ◽  
Apoptosis Index

IntroductionIt has been reported that the NF-κB and MMP-9 signaling pathways were involved in the pathogenesis of osteoarthritis (OA), while the treatment of OA by YSY01 could inhibit the proteasome activity. Therefore, we aimed to study the therapeutic effect of YSY01A treatment on OA via interfering with expression of NF-κB and MMP-9.Material and methodsWestern blot analysis and immunohistochemistry (IHC) assays were used to measure the expression of NF-κB and MMP-9 in animal models established via SH treatment or cellular models established via sodium nitroprusside (SNP) treatment. MTT assay and flow cytometry analysis were performed to observe the effect of YSY01 treatment on cell viability and apoptosis.ResultsThe decreased expression of NF-κB and MMP-9 was observed in OA rabbits and cells treated by YSY01A, thus indicating the inhibitory effect of YSY01A on NF-κB and MMP-9 expression. And YSY01A exhibited a positive therapeutic effect on OA both in vivo and in vitro by inhibiting the expression of NF-κB and MMP-9. Meanwhile, YSY01A treatment could increase cell viability to a certain degree and decrease the apoptosis index, which suggested the application of YSY01A in OA therapy.ConclusionsThe levels of NF-κB and MMP-9 which were associated with aggravated apoptosis were up-regulated in OA models in vivo and in vitro. YSY01A treatment could down-regulate the expression of NF-κB and MMP-9 and inhibit cell apoptosis, thus reducing the severity of OA.

scholarly journals Human levator veli palatini muscle: a novel source of mesenchymal stromal cells for use in the rehabilitation of patients with congenital craniofacial malformations

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Franco Bueno ◽  
Gerson Shigueru Kabayashi ◽  
Carla Cristina Gomes Pinheiro ◽  
Daniela Y. S. Tanikawa ◽  
Cassio Eduardo Raposo-Amaral ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cleft Palate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Osteogenic Potential ◽  
Flow Cytometry Analysis ◽  
Non Invasive ◽  
Levator Veli Palatini

Abstract Background Bone reconstruction in congenital craniofacial differences, which affect about 2–3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stromal cells in regenerative medicine protocols has opened a new field of investigation aimed at finding optimal sources of multipotent cells that can be isolated via non-invasive procedures. In this study, we analyzed whether levator veli palatini muscle fragments, which can be readily obtained in non-invasive manner during palatoplasty in cleft palate patients, represent a novel source of MSCs with osteogenic potential. Methods We obtained levator veli palatini muscle fragments (3–5 mm3), during surgical repair of cleft palate in 5 unrelated patients. Mesenchymal stromal cells were isolated from the muscle using a pre-plating technique and other standard practices. The multipotent nature of the isolated stromal cells was demonstrated via flow cytometry analysis and by induction along osteogenic, adipogenic, and chondrogenic differentiation pathways. To demonstrate the osteogenic potential of these cells in vivo, they were used to reconstruct a critical-sized full-thickness calvarial defect model in immunocompetent rats. Results Flow cytometry analysis showed that the isolated stromal cells were positive for mesenchymal stem cell antigens (CD29, CD44, CD73, CD90, and CD105) and negative for hematopoietic (CD34 and CD45) or endothelial cell markers (CD31). The cells successfully underwent osteogenic, chondrogenic, and adipogenic cell differentiation under appropriate cell culture conditions. Calvarial defects treated with CellCeram™ scaffolds seeded with the isolated levator veli palatini muscle cells showed greater bone healing compared to defects treated with acellular scaffolds. Conclusion Cells derived from levator veli palatini muscle have phenotypic characteristics similar to other mesenchymal stromal cells, both in vitro and in vivo. Our findings suggest that these cells may have clinical relevance in the surgical rehabilitation of patients with cleft palate and other craniofacial anomalies characterized by significant bone deficit.

scholarly journals Periplocin Extracted from Cortex Periplocae Induced Apoptosis of Gastric Cancer Cells via the ERK1/2-EGR1 Pathway

2016 ◽  
Vol 38 (5) ◽  
pp. 1939-1951 ◽  
Author(s):  
Lei Li ◽  
Lian-Mei Zhao ◽  
Su-li Dai ◽  
Wen-Xuan Cui ◽  
Hui-Lai Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis

Background/Aims: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. Methods: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. Results: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. Conclusion: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.

scholarly journals Preliminary study of the toxicity and radioprotective effects of zymosan in vitro and in vivo

2020 ◽  
Author(s):  
Yue-zhi Zhang ◽  
Shu-jing Ge ◽  
Qing-zhen Leng ◽  
Jian-jun Ma ◽  
Hanchen Liu
Keyword(s):  
Flow Cytometry ◽  
Protective Effect ◽  
Cell Viability ◽  
Treatment Time ◽  
Positive Control ◽  
Radioprotective Effect ◽  
X Rays ◽  
Spleen Index

Abstract Background: This study aimed to confirm the cytotoxicity of zymosan in AHH-1 cells and HIECs and to determine the treatment time and dose of zymosan at which it exerts radioprotective effects.Methods: AHH-1 cells and HIECs were administered 0, 20, 40, 80 or 160 μg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 μg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 μg/mL LPS as a positive control. In vivo, weight, the spleen index and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20 and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8 or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, spleen index and thymus index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control. Results: The viability and apoptosis of cells treated with different doses of zymosan for different treatment times were not different from those of control cells (p<0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p<0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p<0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p<0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The radioprotective effect of zymosan was better than that of LPS pretreatment (p<0.05). Conclusion: Zymosan is nontoxic to cells and exerts a better radioprotective effect than LPS.

scholarly journals Evaluation of chidamide and PFI-1 as a combination therapy for triple-negative breast cancer

2020 ◽  
Vol 19 (2) ◽  
pp. 259-264
Author(s):  
Nong Lin ◽  
Qiaolu Yang ◽  
Tong Xu ◽  
Lianguo Shi
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cell Viability ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Histone Deacetylases ◽  
Triple Negative ◽  
Inhibitory Effect

Purpose: To evaluate the in vitro and in vivo effects of the combination therapy of histone deacetylases (HDAsC) inhibitor, chidamide, and bromodomain-containing proteins (BETs) inhibitor, PFI-1, on triplenegative breast cancer (TNBC). Methods: Four distinct breast cancer cell lines and one TNBC mouse model were treated with vehicle, chidamide, PFI-1 alone, or chidamide and PFI-1. The inhibitory effect of chidamide or PFI-1 on HDACs and BETs was assessed by HDAC enzyme inhibition and AlphaScreen assays. Cell viability was determined by MTT assay while protein expression of p-STAT3 was evaluated by western blotting and immunohistochemistry (IHC) staining assay. Results: Chidamide exerted inhibitory effect on HDACs while PFI-1 inhibited BET proteins. The threedimensional model demonstrated the interactions between chidamide and HDAC2, and between PFI-1 and BRD4. Chidamide or PFI-1 exerted inhibitory effects on breast cancer cell proliferation in vitro. However, the combination of PFI-1 and chidamide significantly inhibit MDA-MB-231 cell viability, and decrease the expression of p-STAT3, when compared to that treated with chidamide or PFI-1 alone. Moreover, the combined inhibitory effect of PFI-1 and chidamide on tumor growth was also found in the in vivo mice experiments. Conclusion: The combination of chidamide and PFI-1 is a potential is a potential therapeutic strategy for the management of TNBC. Keywords: Triple-negative breast cancer, Histone deacetylases, Bromodomain

Preparation of Magnetic Drug Loaded Nanoparticles and Its Anticancer Efficacy Against Nasopharyngeal Carcinoma Cells

2021 ◽  
Vol 13 (5) ◽  
pp. 857-863
Author(s):  
Jingjing Chen ◽  
Cheng Kang
Keyword(s):  
Magnetic Nanoparticles ◽  
Nasopharyngeal Carcinoma ◽  
Therapeutic Effect ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Anticancer Efficacy ◽  
Normal Tissues ◽  
Chemotherapy Agent

As an important drug for the treatment of cancer, cis-diamine dichloroplatinum (CDDP) has poor solubility and antagonistic effect when it is used as a chemotherapy agent alone, leading to the insufficient dose in actual administration. In order to solve the above problems, increase the targeting property of CDDP carrier and prolong the half-life period of CDDP’s sustained-release, it is necessary to design a magnetic nano-carrier for CDDP with magnetic targeting function to reduce the damage of CDDP to normal tissues in vivo and improve the therapeutic effect of cancer. Carboxymethyl chitosan (CMCS) is used to directly coat oleic acid (OA)-modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) to create the nano-scale CMCS magnetic nanoparticles (CMCS/OA-Fe2O3 NPs), and CDDP loaded magnetic nanoparticles (CMCS/OA-Fe2O3 NPs/CDDP) are prepared by the bonding interaction between carboxyl groups on the surface of CMCS and the anticancer drug CDDP. The magnetic drug loaded nanoparticles are characterized, and the results show that the magnetic nanoparticles are successfully embedded in CMCS and loaded with CDDP, with the drug load of 43.65 ± 2.37%. MTT assay, flow cytometry and invasion assay are applied to evaluate the inhibitory effect of magnetic drug loaded nanoparticles to nasopharyngeal carcinoma (NPC) cells HNE-1. The results suggest that the magnetic drug loaded nanoparticles successfully prepared have significant inhibitory effect on HNE-1 cells in vitro. Therefore, the magnetic drug loaded nanoparticles prepared have a good therapeutic effect on NPC.

scholarly journals Preliminary study of the toxicity and radioprotective effects of zymosan in vitro and in vivo

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yue-zhi Zhang ◽  
Shu-jing Ge ◽  
Qing-zhen Leng ◽  
Jian-jun Ma ◽  
Han-chen Liu
Keyword(s):  
Flow Cytometry ◽  
Protective Effect ◽  
Cell Viability ◽  
Treatment Time ◽  
Survival Rates ◽  
Positive Control ◽  
X Rays ◽  
Spleen Index

Abstract Background This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and the dose of zymosan. Methods AHH-1 cells and HIECs were administered by 0, 20, 40, 80 or 160 μg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate the cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 μg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 μg/mL LPS. In vivo, weight, the spleen index, and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20, and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8, or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, organ index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control. Results The viability and apoptosis of cells treated with different doses and treatment times of zymosan were not different from those of control cells (p < 0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p < 0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p < 0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p < 0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The survival curves in the irradiated rats were barely separated between the LPS treatment and zymosan treatment. Conclusion Zymosan administration before radiation exposure significantly increased cell viability and the survival rates of rats.

scholarly journals Targeted imaging of esophageal adenocarcinoma with a near-infrared fluorescent peptide

2020 ◽  
Author(s):  
Xiaoyu Kang ◽  
Meng Li ◽  
Lei Liu ◽  
Shaopeng Liu ◽  
Hao Hu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Esophageal Carcinoma ◽  
Esophageal Adenocarcinoma ◽  
Tumor Targeting ◽  
Confocal Imaging ◽  
Block Group ◽  
Flow Cytometry Analysis ◽  
Fluorescent Peptide

Abstract Background: Targeted optical imaging offers a noninvasive and accurate method for the early detection of gastrointestinal tumors, especially for flat appearances. In our previous study, a sequence of SNFYMPL (SNF) was identified as a specific peptide to bind to esophageal carcinoma using phage-display technology. This study aimed to evaluate the tumor-targeting efficacy of Cy5.5-conjugated SNF probe for imaging of esophageal carcinoma in vitro and in vivo.Methods: The SNF-Cy5.5 probe was synthesized and then identified using High Performance Liquid Chromatography (HPLC) and mass spectrometry (MS). Confocal fluorescence imaging and Flow cytometry analysis were performed to evaluate the binding specificity and the receptor binding affinity of SNF-Cy5.5 to OE33. In vivo imaging was performed to evaluate the targeting ability of SNF-Cy5.5 to esophageal carcinoma.Results：The confocal imaging and flow cytometry analysis showed that SNF-Cy5.5 bound specifically to the plasma membrane of OE33 cells with a high affinity. In vivo, for non-block group, SNF-Cy5.5 probe exhibited rapid OE33 tumor targeting during 24 h p.i. and excellent tumor-to-background contrast at 2 h p.i. For the block group, SNF-Cy5.5 was not observed in the mice after 4h p.i. Ex vivo imaging also revealed that a higher fluorescent signal intensity value of the tumors was clearly observed in the non-block group than that in the block group (2.6 ± 0.32× 109 vs 0.8 ± 0.08× 109, p < 0.05).Conclusions: SNF -Cy5.5 was synthesized and characterized with a high efficiency and purity. The higher affinity, specificity, and tumor targeting efficacy of SNF-Cy5.5 were confirmed by in vitro and in vivo tests. SNF-Cy5.5 is a promising optical probe for the imaging of esophageal adenocarcinoma.

The Anticancer Effect of Huaier Extract in Renal Cancer 786-O Cells

Pharmacology ◽  
2018 ◽  
Vol 102 (5-6) ◽  
pp. 316-323 ◽  
Author(s):  
Can Wei ◽  
Zhengfang Liu ◽  
Luchao Li ◽  
Yanbin Zhang ◽  
Zhiqing Fang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Renal Cancer ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Dependent Manner ◽  
Anticancer Effect ◽  
Invasion And Migration ◽  
Underlying Mechanisms

Background: Trametes robiniophila Murr (Huaier) has been used as an adjuvant therapy of tumor in traditional Chinese medicine for many years, but the underlying mechanisms are largely unknown. In the present study, we tested the inhibitory effect of Huaier extract on renal cancer 786-O cells and explored the possible mechanisms. Methods: 786-O cells were treated by gradient concentrations of Huaier extract, cell viability, invasion, migration and apoptosis were assessed by cell counting kit 8, cell scratch, transwell, and flow cytometry assay in vitro. The changes in protein level were detected by western blot analysis. Finally, the anticancer effect of Huaier was tested in vivo by nude mouse tumorigenicity assay. Results: Viability of 786-O cells was suppressed by Huaier in a time- and dose-dependent manner; cell invasion and migration were also dramatically inhibited. Flow cytometry assays showed that Huaier could induce cell apoptosis. Western blotting analysis indicated that Huaier suppressed the activation of PI3K/AKT/mTOR/p70S6K/4E-BP1 signaling pathway. We also found that Huaier could partly reverse the epithelialmesenchymal transition (EMT) process. In vivo experiment indicated that tumor growth in the xenograft mouse model was suppressed by Huaier. Conclusion: Huaier plays an anticancer effect partially through the suppression of the PI3K/AKT/mTOR/p70S6K/4E-BP1 pathway and by reversing the EMT process. Huaier may act as an effective agent for treating renal cell carcinoma.

scholarly journals Preliminary study of the toxicity and radioprotective effects of zymosan in vitro and in vivo

2021 ◽  
Author(s):  
Yue-zhi Zhang ◽  
Shu-jing Ge ◽  
Qing-zhen Leng ◽  
Jian-jun Ma ◽  
Hanchen Liu
Keyword(s):  
Flow Cytometry ◽  
Protective Effect ◽  
Cell Viability ◽  
Treatment Time ◽  
Survival Rates ◽  
Positive Control ◽  
X Rays ◽  
Spleen Index

Abstract Background: This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and dose of zymosan.Methods: AHH-1 cells and HIECs were administered by 0, 20, 40, 80 or 160 μg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate the cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 μg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 μg/mL LPS. In vivo, weight, the spleen index and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20 and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8 or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, organ index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control. Results: The viability and apoptosis of cells treated with different doses and treatment times of zymosan were not different from those of control cells (p<0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p<0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p<0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p<0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The survival curves in the irradiated rats were barely separated between the LPS treatment and zymosan treatment. Conclusion: Zymosan administration before radiation exposure significantly increased cell viability and the survival rates of rats.

Alpha Lipoic Acid (ALA) Inhibits the Anti-Myeloma Effects of Bortezomib.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3832-3832 ◽  
Author(s):  
Jeffrey A Steinberg ◽  
Jing Shen ◽  
Eric Sanchez ◽  
Haiming Chen ◽  
Zhi-Wei Li ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Vascular Dysfunction ◽  
Single Agent ◽  
Inhibitory Effect ◽  
Control Group ◽  
Treatment Schedule ◽  
20 Nm

Abstract Abstract 3832 Poster Board III-768 Introduction ALA is an antioxidant often used in the management of peripheral neuropathy (PN) for patients with multiple myeloma (MM). A clinical trial evaluating ALA in diabetic neuropathy showed this drug to be effective for patients with both somatic and autonomic neuropathies. It also normalized the endoneural blood flow, reduced oxidative stress and improved vascular dysfunction. Bortezomib (Velcade®), the first-in-class proteasome inhibitor (PI), which is approved for the treatment of patients with MM, may cause PN. As a result, patients are often treated empirically with ALA. In this study, we investigated whether ALA has any impact on the anti-MM effects of bortezomib. Methods First, cells from the MM cell lines RPMI8226 and MM1S (1×105 cells per 100μl) were treated with ALA alone to determine whether ALA had any effects on their growth as determined with an MTS assay. MM cells were plated in a 96-well plate using serum-free media. The cells were treated with either media alone or ALA at concentrations ranging from 1 to 1000 μM for 48 hours. The acidity of ALA at these doses was determined and if the pH was less than 7, we neutralized it using NaOH. Second, we measured the proliferation of cells exposed to bortezomib alone and combinations of a fixed concentration of bortezomib and escalating concentrations of ALA. Results The exposure of cells to ALA alone had a stimulatory effect on the growth of both MM cell lines in vitro. ALA alone at 1000 μM resulted in an increase in cell viability of MM1S cells by approximately 10% when compared to the control group. ALA alone also stimulated the growth of RPMI8226 cells but at much lower concentrations than observed for MM1S. Compared to untreated cells, there was an increase in cell viability with ALA at concentrations as low as 1 μM and a concentration dependent increase at concentrations of 1, 10, 100, and 1000 μM in RPMI8226 cells. At the highest concentration (1000 μM) of ALA, cell viability increased 150% when compared to RPMI8226 cells incubated with media alone. Next, we evaluated the effect of ALA on bortezomib's anti-MM activity. As a single agent, bortezomib reduced MM1S (20 nM) and RPMI8226 (5 nM) cell viability by 93% and 70% respectively. When ALA was added at a clinically achievable concentration (100 μM) to bortezomib (RPMI8226, 5 nM; MM1S, 20 nM), a reduction in the anti-MM effects of bortezomib on these cell lines was observed when compared to bortezomib treatment alone. Compared to bortezomib alone, the combination of ALA plus bortezomib doubled cell viability (increased RPMI8226 and MM1S cell viability from 32.5% to 65% and 7.5% to 15%, respectively). These negative effects of ALA on bortezomib's anti-MM activity were consistently observed in multiple experiments involving both of these cell lines evaluating concentrations of ALA ranging from 100 to 1000 μM and bortezomib ranging from 5 to 20 nM. Conclusions Our data suggest that ALA has the potential to antagonize the anti-MM effects of bortezomib based on our in vitro results using MM cell lines. Thus, it is possible that ALA could negatively impact the therapeutic benefit of bortezomib for MM patients and this requires further study especially if ALA is accepted as an intervention in bortezomib-related neuropathy. We are currently completing studies evaluating primary MM patients' tumor cells in vitro and our human MM xenograft models in vivo to further validate this impact of ALA on bortezomib's anti-MM activity and whether changes in treatment schedule of these drugs may prevent this inhibitory effect from occurring. In addition, because part of bortezomib's anti-tumor effects are related to reactive oxygen species (ROS) levels, we are evaluating whether the inhibitory effects of ALA on this PI may be overcome by increasing intracellular ROS levels. Disclosures: Hilger: Millennium Pharmaceutcals: Employment. Berenson:Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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