Chen Lu, Jiang Ke, Jiang Hua, Wei Peng
Orthopedics Department, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Orthopedics Department, Second People's Hospital of Chengdu, Chengdu, Sichuan 610017, P.R. China.
Exp Ther Med. 2014 Aug;8(2):527-532. doi: 10.3892/etm.2014.1752. Epub 2014 Jun 2.
Frequent acquisition of drug resistance is often associated with the chemotherapy of malignant tumors, including osteosarcoma. A number of studies have demonstrated a critical role for autophagy in osteosarcoma development, therapy and drug resistance. However, the molecular mechanisms underlying the autophagy-mediated chemotherapy resistance of osteosarcoma cells remain largely unknown. In the present study, we determined the autophagy and microRNA-155 (miR-155) expression induced by chemotherapeutic drugs in osteosarcoma cells. Then we determined the promotory role of miR-155 to the chemotherapy-induced autophagy. Our results demonstrated that microRNA-155 (miR-155) expression was highly induced during chemotherapy of osteosarcoma cells, and this was accompanied by upregulated autophagy. The increased miR-155 expression levels upregulated anticancer drug-induced autophagy in osteosarcoma cells and ameliorated the anticancer drug-induced cell proliferation and viability decrease. Therefore, the results of the present study demonstrated that miR-155 mediated drug-resistance in osteosarcoma cells by inducing autophagy. The present study recognized a novel mechanism of chemoresistance in osteosarcoma cancers.
耐药性的频繁获得通常与包括骨肉瘤在内的恶性肿瘤化疗相关。许多研究已证明自噬在骨肉瘤的发生、治疗及耐药性中起关键作用。然而,骨肉瘤细胞自噬介导的化疗耐药性的分子机制仍 largely 未知。在本研究中,我们测定了化疗药物在骨肉瘤细胞中诱导的自噬及 microRNA-155(miR-155)表达。然后我们确定了 miR-155 对化疗诱导自噬的促进作用。我们的结果表明,在骨肉瘤细胞化疗期间,microRNA-155(miR-155)表达被高度诱导,并且这伴随着自噬上调。miR-155 表达水平的增加上调了骨肉瘤细胞中抗癌药物诱导的自噬,并改善了抗癌药物诱导的细胞增殖和活力下降。因此,本研究结果表明 miR-155 通过诱导自噬介导骨肉瘤细胞中的耐药性。本研究识别出了骨肉瘤癌症中一种新的化疗耐药机制。