Ad5-EMC6 mediates antitumor activity in gastric cancer cells through the mitochondrial apoptosis pathway

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.

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Antitumor activity of SA12, a novel peptide, on SKBr-3 breast cancer cells via the mitochondrial apoptosis pathway

Drug Design Development and Therapy ◽

10.2147/dddt.s75780 ◽

2015 ◽

pp. 1319 ◽

Cited By ~ 1

Author(s):

Huizhong Zhang ◽

Longfei Yang ◽

Ying Cui ◽

Jianjun Shen ◽

Fang Lin ◽

...

Keyword(s):

Breast Cancer ◽

Antitumor Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mitochondrial Apoptosis ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway

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miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin

Cellular Physiology and Biochemistry ◽

10.1159/000495867 ◽

2018 ◽

Vol 51 (5) ◽

pp. 2212-2223 ◽

Cited By ~ 6

Author(s):

Shuning Xu ◽

Danyang Li ◽

Tianyuan Li ◽

Lei Qiao ◽

Ke Li ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Gastric Cancer Cells ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Reporter Assays ◽

Trail Sensitivity

Background/Aims: TNF-related apoptosis-inducing ligand (TRAIL) is a novel and low-toxic anti-tumor drug used for various cancers. However, cancer cells usually develop mechanisms to acquire the resistance against TRAIL. Among these changes, dysregulation of microRNAs (miRNAs) usually occurs in cancer cells and is responsible for induction of drug resistance. Methods: Expression of miR-494 in gastric cancer tissues and cell lines was detected by quantitative reverse transcriptase real time PCR (qRT-PCR) analysis. Effect of miR-494 on regulating the TRAIL sensitivity to gastric cancer cell lines was evaluated by MTT assays. Bioinformatics and luciferase reporter assays were used to confirm the regulation of miR-494 on survivin. Mitochondrial apoptosis pathway in gastric cancer cells was tested by western blot and flow cytometry analysis. Results: Obvious downregulation of miR-494 was observed in gastric cancer cells. Furthermore, we found that expression profile of miR-494 was associated with TRAIL-sensitivity in gastric cancer. Enforced expression of miR-494 was found to sensitize the gastric cancer cells to TRAIL-induced cytotoxicity. Mechanically, Luciferase reporter assays proved that survivin was the target of miR-494 in gastric cancer cells. Enforced expression of miR-494 decreased the expression of survivin, and thus promoted the TRAIL-induced mitochondria collapse and apoptosis pathway. Conclusion: MiR-494/survivin axis represents a potential mechanism which is responsible for TRAIL resistance in gastric cancer cells. Increasing the miR-494 expression may serve as a novel therapeutic strategy to sensitize gastric cancer cells to TRAIL treatment.

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