Paclitaxel inhibits proliferation and promotes apoptosis through regulation ROS and endoplasmic reticulum stress in oste
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ORIGINAL ARTICLE
Paclitaxel inhibits proliferation and promotes apoptosis through regulation ROS and endoplasmic reticulum stress in osteosarcoma cell Ming Li1 · Liming Yin1 · Lili Wu1 · Yunsen Zhu1 · Xi Wang1 Received: 6 March 2020 / Accepted: 17 June 2020 © The Korean Society of Toxicogenomics and Toxicoproteomics 2020 2020
Abstract Background Paclitaxel is a chemotherapeutic drug for cancer, which is isolated from the Pacific yew tree. However, and the molecular mechanism and the antitumor effects of paclitaxel on osteosarcoma cell remain to be explored. Objective The aim of our study was to explore the possible molecular mechanisms of apoptosis in osteosarcoma induced by paclitaxel. Results Paclitaxel can obviously decrease the proliferation of HOS-732 cells in a dose-dependent manner. Paclitaxel could induce the cell cycle arrest at the G2/M-phase and decreases the CDK5 and CCNE1 expression in HOS-732 cells. Paclitaxel promotes cell apoptosis in HOS-732 cells, which may be contacted to the decreasing of Bcl-2 protein expression. Further, the production of ROS in HOS-732 cells was remarkably increased with the increasing concentration of paclitaxel. Moreover, paclitaxel induces the ER-stress related gene and protein expression (GRP79, DDIT3 mRNA and GRP78, XBP-1 s, IRE1α protein expression) in osteosarcoma cells. Conclusion Paclitaxel can inhibit the proliferation of HOS-732 cells and increase ROS and ER-stress response to promote cell apoptosis, suggesting that paclitaxel may represent a new therapeutic option for the treatment and prevention osteosarcoma. Keywords Paclitaxel · Reactive oxygen species · COX-2 · Osteosarcoma
Introduction Osteosarcoma is one of the common malignant bone tumor occurring usually in adolescents. Early symptoms of osteosarcoma include pain, lumps, junction dysfunction, fractures and other irritative symptoms (Gibbs et al. 2002). Currently, the main treatments for osteosarcoma are surgical resection neoadjuvant chemotherapy, and chemotherapy again adding surgery. The 5-year survival rate in osteosarcoma is approximately 60–70%, and there are about 40–50% of patients having pulmonary metastasis (Mcguire et al. 2017; Vos et al. 2016). Hence, it is very urgent to develop new therapies improving the prognosis of osteosarcoma patients.
Ming Li, Liming Yin, Lili Wu: Contributed equally to this work. * Xi Wang [email protected] 1
The First People’s Hospital of Wenling, No. 333 Chuan’an Southern Road, Cheng xi Street, Wenling 317500, China
Paclitaxel is a chemotherapeutic drug for cancer, which is isolated from the Pacific yew tree (Shakhwar et al. 2020; Martino et al. 2020). It is well-documented to have cytotoxic activity against several tumors including gastric cancer, breast cancer, lung cancer, ovarian cancer and colorectal cancer (Otsuka et al. 2020; Goldman et al. 2019; Schmid et al. 2020; Weng et al. 2015; Zhong et al. 2019). A studies have suggested that chemotherapeutic drugs inhibit the growth of cancerous tissue through promoting cell apoptosis (Saad and Abdel-Rah
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