Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate

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WORLD JOURNAL OF SURGICAL ONCOLOGY

RESEARCH

Open Access

Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate Liangdong Jiang1, Cheng Tao1, Aiyong He1 and Xiaojie He2*

Abstract Background: miR-126 plays an important role in the proliferation, invasion, migration, and chemotherapeutics resistance in cancer. Epigallocatechin-3-gallate (EGCG), as the major polyphenolic constituent present in green tea, is a promising anticancer agent. However, the role of miR-126 in EGCG anticancer remains unclear. Here, we investigated the effects of miR-126 and EGCG on cell viability, apoptosis, cell cycle distribution of osteosarcoma cells and the sensitization of miR-126 on osteosarcoma cells to EGCG. Methods: The cell viability, apoptosis and cycle distribution were analyzed using MTT assay and flow cytometry. Results: Our results showed that EGCG (0.025, 0.05, 0.1, 0.2 g/L) suppresses proliferation of osteosarcoma MG63 and U2OS cells in a concentration-dependent and time-dependent manner and the inhibitory effects of 0.05 g/L EGCG on U2OS cells were roughly equivalent to 20 μM cisplatin (DDP); miR-126 could promote apoptosis and inhibit proliferation in U2OS cells but without significant effects on cell cycle G1 phase arrest; EGCG suppressed proliferation of U2OS cells through induction of cell cycle G1 arrest and apoptotic death; overexpression of miR-126 enhanced the inhibitory effects of EGCG on proliferation in U2OS cells via promotion of apoptosis. Conclusions: Our results demonstrate that enhanced expression of miR-126 increased the sensitivity of osteosarcoma cells to EGCG through induction of apoptosis. Keywords: Osteosarcoma, miR-126, Epigallocatechin-3-gallate, Sensitization, Apoptosis

Background Osteosarcoma is a primary malignant bone tumor with high morbidity that occurs mainly in children and adolescents. Multiple options for the treatment of osteosarcoma have been described, including chemotherapy, radiation, and so on, however, therapeutic efficacy is typically transient and mostly absent with advanced disease [1]. Therefore, the need for more rational approaches to osteosarcoma therapy is essential. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea, showing anti-inflammatory, antioxidant, anticancer and immunomodulatory activities [2-5]. It has been shown that EGCG has extensive anticancer activities, including in breast cancer [6], cervical cancer [7], * Correspondence: [email protected] 2 Children’s Medical Center, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, Hunan 410011, P.R. China Full list of author information is available at the end of the article

lung cancer [8], prostate cancer [9], colon cancer [10], head and neck cancer [11], gastric cancer [12], ovarian cancer [13], even cancer stem cells [14], and so on. It was reported that combined administration of EGCG and interleukin 1 (IL-1) receptor antagonist could efficiently decrease IL-1-induced tumorigenic factors, leading