Department of General Surgery, The Second Affiliated Hospital of South-east University, The Second Hospital of Nanjing, Nanjing 210003, P.R. China.
Mol Med Rep. 2013 Feb;7(2):642-8. doi: 10.3892/mmr.2012.1191. Epub 2012 Nov 21.
MicroRNA-27a (miR‑27a) is an oncogene that contributes to drug resistance in various types of cancer. However, the involvement of miR‑27a in gastric cancer has yet to be elucidated. Perifosine is an alkylphospholipid exhibiting antitumor activity as shown in both preclinical studies and clinical trials. The effects of perifosine on gastric cancer have yet to be determined. Therefore, this study was conducted to detect the role of miR‑27a and perifosine in human gastric cancer. miR‑27a was found to be expressed in human gastric cancer tissues and cell lines by quantitative reverse-transcription polymerase chain reaction (qRT‑PCR). The correlation between miR‑27a expression and clinicopathological characteristics of gastric cancer. We also explored the growth inhibitory effect of perifosine on human gastric cancer cells with or without co‑targeting miR‑27a by sulforhodamine B (SRB) assay. The results showed that miR‑27a expression was significantly upregulated in gastric cancer tissues, compared with their non‑tumor adjacent tissues. High expression levels of miR‑27a were associated with poor tumor histological grade (P=0.037). MiR‑27a inhibitors suppressed the growth of MGC‑803 cells. Assay results showed that perifosine exerted its activity selectively on the AGS cell line and the growth inhibitory effect of perifosine was enhanced significantly in combination with miR‑27a inhibitors in MGC‑803 cells. In conclusion, our results demonstrated that miR‑27a may be a therapeutic target and potential prognostic biological marker in gastric cancer. MiR‑27a inhibitors alone or in combination with perifosine may be a novel therapeutic approach against gastric cancer.
微小 RNA-27a (miR-27a) 是一种癌基因，它导致多种类型癌症的耐药性。然而，miR-27a 在胃癌中的作用尚未阐明。培非司亭是一种烷基磷脂，具有抗肿瘤活性，已在临床前研究和临床试验中得到证实。培非司亭对胃癌的作用尚未确定。因此，本研究旨在检测 miR-27a 和培非司亭在人胃癌中的作用。通过定量逆转录聚合酶链反应 (qRT-PCR) 发现 miR-27a 在人胃癌组织和细胞系中表达。分析 miR-27a 表达与胃癌临床病理特征的相关性。我们还通过磺酰罗丹明 B (SRB) 试验探讨了培非司亭对人胃癌细胞的生长抑制作用，以及同时靶向 miR-27a 对其的影响。结果表明，miR-27a 在胃癌组织中的表达明显上调，与非肿瘤相邻组织相比。miR-27a 高表达与肿瘤组织学分级差相关 (P=0.037)。miR-27a 抑制剂抑制了 MGC-803 细胞的生长。结果表明，培非司亭对 AGS 细胞系具有选择性活性，并且与 miR-27a 抑制剂联合使用时，MGC-803 细胞的生长抑制作用显著增强。总之，我们的研究结果表明，miR-27a 可能是胃癌的治疗靶点和潜在的预后生物标志物。miR-27a 抑制剂单独或联合培非司亭可能是治疗胃癌的新方法。
