title: Inhibition of autophagy enhances cisplatin-induced apoptosis in the MG63 human osteosarcoma cell line.
abstract: Autophagy is a significant catabolic process that allows the renewal of intracellular organelles, through which cells are able to maintain homeostasis. In addition, autophagy may be associated with the carcinogenesis of osteosarcoma (OS). Cisplatin (CDDP) is an alkylating agent that is commonly used as an anticancer therapy. However, the pathways underlying the effects of CDDP remain to be elucidated. The present study demonstrated that 3-methyladenine (3-MA), an inhibitor of autophagy, was able to increase the proliferation inhibition ratios of MG63 human OS cells when used in combination with CDDP. Furthermore, MG63 cells produced significantly more microtubule-associated protein light chain 3II (LC3II), a widely used marker for monitoring autophagy, following CDDP treatment. Treatment with 3-MA was observed to inhibit these changes. Similarly, MG63 cells co-treated with 3-MA and CDDP demonstrated increased sensitivity to CDDP-induced apoptosis, compared with those exposed to CDDP alone. The present study revealed variation in the expression of LC3II and caspase-3 activity following treatment with certain drugs. The results of the present study suggest that CDDP may be capable of inducing apoptosis and autophagy, and that autophagy may be able to inhibit apoptosis in MG63 cells. Therefore, downregulation of autophagy may increase the chemotherapeutic sensitivity of MG63 cells to CDDP.
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Zengwu
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
keywords: 3-methyladenine; apoptosis; autophagy; cisplatin; osteosarcoma