Xing Chen1, Dongsheng Xiong2, Liya Ye1, Huichun Yang1, Shuangshuang Mei1, Jinhong Wu1, Shanshan Chen1, Ruoran Mi3. 1. Department of Obstetrics and Gynecology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, 317000, Zhejiang, China. 2. State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China. 3. Department of Obstetrics and Gynecology, General Hospital of Tianjin Medical University, No. 154 Anshan Road, Heping District, Tianjin, 300052, China. zhengyongfatijmu@163.com.
Abstract
PURPOSE: Cisplatin (DDP)-based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. In the present study, we aimed to explore the effects of SPP1 on the proliferation and apoptosis rate of the HeLa cervical cancer cell line with cisplatin (DDP) resistance. METHODS: Microarray analysis was employed to select differentially expressed genes in cervical cancer tissues and adjacent tissues. Then, we established a DDP-resistant HeLa cell line (res-HeLa). Western blotting was used to detect SPP1 expression in both tissue and cells. After the transfection with si-SPP1 and pcDNA3.1-SPP1, colony formation and MTT assays were applied to detect cell proliferation changes. Flow cytometry was employed to detect the cell apoptosis rate. Western blotting was performed to verify the activation of PI3K/Akt signal pathway proteins related to DDP resistance. RESULTS: SPP1 was overexpressed in cervical cancer tissues and cell lines. Compared to normal HeLa cells, expression of SPP1 was significantly enhanced in res-HeLa cells. SPP1 knockdown resulted in repressed proliferation and enhanced apoptosis of res-HeLa cells, which could be reversed by SPP1 overexpression in HeLa cells. Additionally, downregulation of SPP1 improved the DDP sensitivity of HeLa by inhibiting the PI3K/Akt signaling pathway. CONCLUSION: SPP1 inhibition could suppress proliferation, induce apoptosis and increase the DDP chemo-sensitivity of HeLa cells.
PURPOSE:Cisplatin (DDP)-based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. In the present study, we aimed to explore the effects of SPP1 on the proliferation and apoptosis rate of the HeLa cervical cancer cell line with cisplatin (DDP) resistance. METHODS: Microarray analysis was employed to select differentially expressed genes in cervical cancer tissues and adjacent tissues. Then, we established a DDP-resistant HeLa cell line (res-HeLa). Western blotting was used to detect SPP1 expression in both tissue and cells. After the transfection with si-SPP1 and pcDNA3.1-SPP1, colony formation and MTT assays were applied to detect cell proliferation changes. Flow cytometry was employed to detect the cell apoptosis rate. Western blotting was performed to verify the activation of PI3K/Akt signal pathway proteins related to DDP resistance. RESULTS:SPP1 was overexpressed in cervical cancer tissues and cell lines. Compared to normal HeLa cells, expression of SPP1 was significantly enhanced in res-HeLa cells. SPP1 knockdown resulted in repressed proliferation and enhanced apoptosis of res-HeLa cells, which could be reversed by SPP1 overexpression in HeLa cells. Additionally, downregulation of SPP1 improved the DDP sensitivity of HeLa by inhibiting the PI3K/Akt signaling pathway. CONCLUSION:SPP1 inhibition could suppress proliferation, induce apoptosis and increase the DDP chemo-sensitivity of HeLa cells.
Authors: William L Hwang; Karthik A Jagadeesh; Jimmy A Guo; Hannah I Hoffman; Payman Yadollahpour; Jason W Reeves; Rahul Mohan; Eugene Drokhlyansky; Nicholas Van Wittenberghe; Orr Ashenberg; Samouil L Farhi; Denis Schapiro; Prajan Divakar; Eric Miller; Daniel R Zollinger; George Eng; Jason M Schenkel; Jennifer Su; Carina Shiau; Patrick Yu; William A Freed-Pastor; Domenic Abbondanza; Arnav Mehta; Joshua Gould; Conner Lambden; Caroline B M Porter; Alexander Tsankov; Danielle Dionne; Julia Waldman; Michael S Cuoco; Lan Nguyen; Toni Delorey; Devan Phillips; Jaimie L Barth; Marina Kem; Clifton Rodrigues; Debora Ciprani; Jorge Roldan; Piotr Zelga; Vjola Jorgji; Jonathan H Chen; Zackery Ely; Daniel Zhao; Kit Fuhrman; Robin Fropf; Joseph M Beechem; Jay S Loeffler; David P Ryan; Colin D Weekes; Cristina R Ferrone; Motaz Qadan; Martin J Aryee; Rakesh K Jain; Donna S Neuberg; Jennifer Y Wo; Theodore S Hong; Ramnik Xavier; Andrew J Aguirre; Orit Rozenblatt-Rosen; Mari Mino-Kenudson; Carlos Fernandez-Del Castillo; Andrew S Liss; David T Ting; Tyler Jacks; Aviv Regev Journal: Nat Genet Date: 2022-07-28 Impact factor: 41.307
Authors: Xuan Yi; Linlin Luo; Yanzhen Zhu; Hong Deng; Huitian Liao; Yang Shen; Yan Zheng Journal: Cancer Cell Int Date: 2022-10-20 Impact factor: 6.429