4.5 Article

MicroRNA-27a inhibitors alone or in combination with perifosine suppress the growth of gastric cancer cells

Journal

MOLECULAR MEDICINE REPORTS
Volume 7, Issue 2, Pages 642-648

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2012.1191

Keywords

microRNA-27a; gastric cancer; perifosine; combination therapy

Funding

  1. 'Medical ZhongDianRenCai Project' of Jiangsu [RC2011059]
  2. 333 Project
  3. 'Six RenCai Gaofeng' Funding for the Young Academic Leader of Jiangsu
  4. National Natural Science 647 Foundation of China [30873099, 81001444]
  5. Science & Technology Development Project of Nanjing [201201055, 2012YX001]

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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.

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