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miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivin pathway

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Tumor Biology

Abstract

The purposes of this study were to determine the expression profiles of microRNA-34a (miR-34a) in human gastric cancer cell line (SGC-7901) and cisplatin-resistant cell lines (SGC-7901/DDP), and to establish the correlation between miR-34a expression profile and the sensitivity of human gastric cancer cell to cisplatin-based pattern, thereby providing new methods and strategies for treating gastric cancer. Gastric cancer cell line (SGC-7901) and cisplatin-resistant cell line (SGC-7901/DDP) were cultivated in vitro, respectively. Quantitative real-time PCR (qRT-PCR) and Western blot were utilized to determine the expression profiles of miR-34a and survivin in both gastric cancer cell lines. With miR-34a mimic and miR-34a inhibitor transfected into SGC-7901 and SGC-7901/DDP for 48 h, post-transfection changes of miR-34a expression was determined; the effects of miR-34a ectopic expression on the viability of cisplatin-induce gastric cancer cell were assayed by the MTT method. The effects of miR-34a ectopic expression on apoptosis of cisplatin-induce gastric cancer cell were determined by Annexin V/propidium iodide (PI) double staining method and flow cytometry. The effects of miR-34a ectopic expression on the AKT and p-AKT expression of cisplatin-induce gastric cancer cells were determined by Western blot and flow cytometry with the PI3K pathway inhibitor Wortmannin. As shown by qRT-PCR and Western blot analyses, the expression of miR-34a in cisplatin-resistant cell lines decreased significantly in comparison to that of SGC-7901 cell line (p < 0.05), while significant up-regulation of survivin expression was also observed (p < 0.05). Compared with the control group, the expression of miR-34a increased significantly in SGC-7901 cells transfected with miR-34a mimic for 48 h (p < 0.01). After miR-34a inhibitor transfection, the expression of miR-34a decreased significantly (p < 0.05). The viability of cisplatin-induce gastric cancer cells increased significantly (p < 0.05) with significant decrease of apoptosis after miR-34a expression inhibition, as demonstrated by MTT and flow cytometry with miR-34a over-expression, the viability of cisplatin-induce gastric cancer cells decreased significantly (p < 0.05), with significant apoptosis increase (p < 0.05). As shown by Western blot and flow cytometry, in comparison to the control group, Wortmannin could inhibit miR-34a inhibitor and DDP induced up-regulation of p-AKT significantly (p < 0.05) and stimulated apoptosis. In conclusion, miR-34a expression was down-regulated in cisplatin-resistant cell lines. miR-34a over-expression could improve the sensitivity of gastric cancer cells against cisplatin-based chemotherapies, with PI3K/AKT/survivin signaling pathway possibly involved in the mechanism.

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Conflicts of interest

The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.

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Authors and Affiliations

  1. Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Weiguo Cao, Hao Li, Jinsong Jiang, Mei Geng & Yening Jin

  2. Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Weiping Yang

  3. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Number 197, Ruijin Er Road, Shanghai, 200025, China

    Rong Fan & Yunlin Wu

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  1. Weiguo Cao
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  2. Weiping Yang
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  3. Rong Fan
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  4. Hao Li
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  5. Jinsong Jiang
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  6. Mei Geng
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  7. Yening Jin
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  8. Yunlin Wu
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Correspondence to Yunlin Wu.

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W. Cao and W. Yang contributed equally to this study.

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Cao, W., Yang, W., Fan, R. et al. miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivin pathway. Tumor Biol. 35, 1287–1295 (2014). https://doi.org/10.1007/s13277-013-1171-7

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  • DOI: https://doi.org/10.1007/s13277-013-1171-7

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