TY - JOUR
T1 - GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin
AU - Gong, Xin
AU - Liu, Jing
AU - Zhang, Dan
AU - Yang, Dawei
AU - Min, Zhihui
AU - Wen, Xiaoxing
AU - Wang, Guifang
AU - Li, Huayin
AU - Song, Yuanlin
AU - Bai, Chunxue
AU - Li, Jing
AU - Zhou, Jian
N1 - Publisher Copyright:
© 2017 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/8
Y1 - 2017/8
N2 - Background and objective: Chemotherapy drugs, such as cisplatin (DDP), improve the survival of patients with lung cancer by inducing apoptosis in cancer cells, which quickly develop resistance to DDP through uncharacterized mechanisms. Glioma Pathogenesis-Related Protein 1 (GLIPR1) plays an important role in cell proliferation, migration and apoptosis. However, the expression and function of GLIPR1 in mediating DDP resistance in human lung adenocarcinoma A549/DDP and human large cell lung cancer H460/DDP cells has not yet been reported. Methods: In this study, real-time PCR (RT-PCR) and western blot were used to examine the mRNA and protein expression of GLIPR1, respectively. Bright-field microscopy, the cell counting kit-8 (CCK-8) assay, flow cytometry analysis and JC-1 dye were used to measure the cellular morphology, proliferation, apoptosis and mitochondrial membrane potential, respectively. Results: Compared to human lung adenocarcinoma A549 cells, the mRNA and protein expression of GLIPR1 were significantly increased in DDP-resistant A549/DDP cells (p < 0.05). Similarly, the mRNA level of GLIPR1 in DDP-resistant H460/DDP cells was also significantly higher than that in DDP-sensitive H460 cells (p < 0.05). Silencing of GLIPR1 in A549/DDP and H460/DDP cells led to increased apoptosis via a mitochondrial signaling pathway following incubation with various concentrations of DDP. Furthermore, GLIPR1 downregulation markedly reduced the protein expression of Bcl-2, and increased the cleaved Poly (ADP-Ribose) Polymerase (PARP) and cleaved caspase-3 in DDP-resistant A549/DDP cells. Conclusion: In this study, we demonstrated for the first time that GLIPR1 could modulate the response of DDP-resistant A549/DDP and H460/DDP cells to cisplatin. Therefore, GLIPR1 deserves further investigation in the context of none-small lung cancer (NSCLC).
AB - Background and objective: Chemotherapy drugs, such as cisplatin (DDP), improve the survival of patients with lung cancer by inducing apoptosis in cancer cells, which quickly develop resistance to DDP through uncharacterized mechanisms. Glioma Pathogenesis-Related Protein 1 (GLIPR1) plays an important role in cell proliferation, migration and apoptosis. However, the expression and function of GLIPR1 in mediating DDP resistance in human lung adenocarcinoma A549/DDP and human large cell lung cancer H460/DDP cells has not yet been reported. Methods: In this study, real-time PCR (RT-PCR) and western blot were used to examine the mRNA and protein expression of GLIPR1, respectively. Bright-field microscopy, the cell counting kit-8 (CCK-8) assay, flow cytometry analysis and JC-1 dye were used to measure the cellular morphology, proliferation, apoptosis and mitochondrial membrane potential, respectively. Results: Compared to human lung adenocarcinoma A549 cells, the mRNA and protein expression of GLIPR1 were significantly increased in DDP-resistant A549/DDP cells (p < 0.05). Similarly, the mRNA level of GLIPR1 in DDP-resistant H460/DDP cells was also significantly higher than that in DDP-sensitive H460 cells (p < 0.05). Silencing of GLIPR1 in A549/DDP and H460/DDP cells led to increased apoptosis via a mitochondrial signaling pathway following incubation with various concentrations of DDP. Furthermore, GLIPR1 downregulation markedly reduced the protein expression of Bcl-2, and increased the cleaved Poly (ADP-Ribose) Polymerase (PARP) and cleaved caspase-3 in DDP-resistant A549/DDP cells. Conclusion: In this study, we demonstrated for the first time that GLIPR1 could modulate the response of DDP-resistant A549/DDP and H460/DDP cells to cisplatin. Therefore, GLIPR1 deserves further investigation in the context of none-small lung cancer (NSCLC).
UR - https://www.scopus.com/pages/publications/85026730348
U2 - 10.1371/journal.pone.0182410
DO - 10.1371/journal.pone.0182410
M3 - Article
C2 - 28771580
AN - SCOPUS:85026730348
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0182410
ER -