Research Article Glucose-Regulated Protein 94 Modulates the Response of Osteosarcoma to Chemotherapy Chien-Yu Huang, 1,2 Po-Li Wei, 1,3,4,5 Jin-Wun Wang, 6 Precious Takondwa Makondi, 7,8 Ming-Te Huang, 1,2 Hsin-An Chen , 1,2 and Yu-Jia Chang 3,7,8 1 Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan 3 Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan 4 Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan 5 Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan 6 Department of Orthopedics, Chiali Chi-Mei Medical Center, Chiali, Tainan, Taiwan 7 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 8 International PhD Program in Medicine, Taipei Medical University, Taipei, Taiwan Correspondence should be addressed to Hsin-An Chen; dtsurga6@gmail.com and Yu-Jia Chang; r5424012@tmu.edu.tw Received 16 April 2018; Revised 19 September 2018; Accepted 16 October 2018; Published 3 January 2019 Guest Editor: Marta Brambilla Copyright © 2019 Chien-Yu Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating the chemo-responsiveness of cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the response of OS to chemotherapy has never been explored. Methods. In this study, two OS cell lines, MG63 and 143B cells, were used to evaluate the mechanism by which GRP94 modulates the response of osteosarcoma to chemotherapy. GRP94-knockdown (GRP94-KD) OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was quantified with propidium iodide (PI) staining and flow cytometry. Results. Silencing of GRP94 in MG63 and 143B cells did not influence the growth and migration of the cells, but reduced the colony formation. GRP94-KD OS cells were more resistant to paclitaxel, gemcitabine, and epirubicin treatments than cells transfected with the scrambled control, and more cells transfected with the scrambled control underwent apoptosis after paclitaxel, gemcitabine, and epirubicin treatments than GRP94-KD cells. Conclusions. Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS. 1. Introduction Osteosarcoma (OS) is the most common type of primary solid malignant bone tumor in children and young adults (nearly 5% of all cases of cancer in children), with 70–75% of cases occurring between the ages of 10 and 25 years [1]. OS forms at the ends of the long bones of the body, such as in the arms and in the legs, mainly near the knee [2]. OS is an aggressive disease with a high recurrence rate after treatment and is highly metastatic to lungs and bones, thus leading to a poor prognosis [1, 3]. Currently, the standard therapeutic strategy for OS is surgical resection Hindawi Disease Markers Volume 2019, Article ID 4569718, 10 pages https://doi.org/10.1155/2019/4569718