title: Overexpression of the regulator of G-protein signaling 5 reduces the survival rate and enhances the radiation response of human lung cancer cells.
abstract: Regulator of G protein signaling 5 (RGS5) belongs to the R4 subfamily of RGS proteins, a family of GTPase activating proteins, which is dynamically regulated in various biological processes including blood pressure regulation, smooth muscle cell pathology, fat metabolism and tumor angiogenesis. Low-expression of RGS5 was reported to be associated with tumor progression in lung cancer. In the present study, we examined the potential roles of RGS5 in human lung cancer cells by overexpressing RGS5 in the cancer cells and further explored the underlying molecular mechanisms. The RGS5 gene was cloned and transfected into the human lung cancer cell lines A549 and Calu-3. The cells were tested for apoptosis with flow cytometry, for viability with MTT, for mobility and adhesion capacity. The radiosensitization effect of RGS5 was measured by a colony formation assay. The mechanisms of RGS5 functioning was also investigated by detection of protein expression with western blot analysis, including PARP, caspase 3 and 9, bax, bcl2, Rock1, Rock2, CDC42, phospho-p53 (Serine 15) and p53. The present study demonstrated that RGS5 overexpression remarkably induced apoptosis in human lung cancer cells, which was suggested to be through mitochondrial mechanisms. Overexpression of RGS5 resulted in significantly lower adhesion and migration abilities of the lung cancer cells (P<0.01). Furthermore, overexpression of RGS5 sensitized the lung cancer cells to radiation. In conclusion, the present study showed that RGS5 played an inhibitory role in human lung cancer cells through induction of apoptosis. Furthermore, RGS5 enhanced the cytotoxic effect of radiation in the human lung cancer cells. Our results indicated that RGS5 may be a potential target for cancer therapy.
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Zumin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524000, P.R. China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524000, P.R. China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Center, Shilong People's Hospital, Dongguan City, Guangdong 523321, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Honglian
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020710:RGS Proteins / Q000096:biosynthesis* / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D020710:RGS Proteins; C491349:RGS5 protein, human