Xiaohong Ruan1, Meigong Zhong2, Wanmin Liu1, Qiongru Liu3, Wenjie Lu4, Yan Zheng5, Xin Zhang3,4. 1. Department of Gynecology, Jiangmen Central Hospital, Jiangmen 529030, China. 2. Department of Pharmacy, Jiangmen Maternity and Child Health Care Hospital, Jiangmen 529000, China. 3. Department of Pathology, Jiangmen Central Hospital, Jiangmen 529030, China. 4. Central Laboratory, Jiangmen Central Hospital, Jiangmen 529030, China. 5. Research and Development Center for Molecular Diagnosis Engineering Technology of Human Papillomavirus (HPV) Related Diseases of Guangdong Province, Chaozhou 521021, China.
Abstract
OBJECTIVE: To investigate the effect of overexpression of leukemia inhibitory factor (LIF) on cisplatin and paclitaxel resistance of endometrial cancer cells in vitro. METHODS: Endometrial cancer cell lines HEC-1B and RL95-2 were infected with a recombinant lentivirus to overexpress LIF, and the changes in LIF expression was verified using RT-qPCR and ELISA. The viability of the LIF-overexpressing cells was assessed using CCK-8 assay, and the cell apoptosis and changes in mitochondrial membrane potential in response to cisplatin or paclitaxel treatment were analyzed with annexin V-FITC/PI staining and JC-1 assay, respectively. The effect of LIF overexpression on the expressions of Bcl-2 family proteins and STAT3 pathway was evaluated using Western blotting; dual-luciferase reporter gene assay was employed to detect the transcriptional activity of STAT3. The effect of STAT3 silencing on apoptosis of the LIF-overexpressing cells induced by cisplatin or paclitaxel was investigated. RESULTS: The cell lines infected with the recombinant lentivirus showed significantly increased mRNA and protein levels of LIF (P < 0.05) without obvious changes in the cell viability (P>0.05). LIF overexpression significantly attenuated cisplatin-or paclitaxel-induced apoptosis of the endometrial cancer cells (P < 0.05) and markedly increased mitochondrial membrane potential of the cells (P < 0.05). The expressions of Bcl-2, Bcl-xL and p-STAT3 proteins increased obviously while the expressions of Bax, Bad and STAT3 either decreased or showed no obvious changes in the LIF-overexpressing cells. Overexpressing LIF significantly enhanced the transcriptional activity of STAT3 (P < 0.05), and silencing STAT3 obviously enhanced apoptosis of the endometrial cancer cells overexpressing LIF (P < 0.05). CONCLUSIONS: s Overexpression of LIF can enhance cisplatin and paclitaxel resistance to endometrial cancer cells in vitro.
OBJECTIVE: To investigate the effect of overexpression of leukemia inhibitory factor (LIF) on cisplatin and paclitaxel resistance of endometrial cancer cells in vitro. METHODS:Endometrial cancer cell lines HEC-1B and RL95-2 were infected with a recombinant lentivirus to overexpress LIF, and the changes in LIF expression was verified using RT-qPCR and ELISA. The viability of the LIF-overexpressing cells was assessed using CCK-8 assay, and the cell apoptosis and changes in mitochondrial membrane potential in response to cisplatin or paclitaxel treatment were analyzed with annexin V-FITC/PI staining and JC-1 assay, respectively. The effect of LIF overexpression on the expressions of Bcl-2 family proteins and STAT3 pathway was evaluated using Western blotting; dual-luciferase reporter gene assay was employed to detect the transcriptional activity of STAT3. The effect of STAT3 silencing on apoptosis of the LIF-overexpressing cells induced by cisplatin or paclitaxel was investigated. RESULTS: The cell lines infected with the recombinant lentivirus showed significantly increased mRNA and protein levels of LIF (P < 0.05) without obvious changes in the cell viability (P>0.05). LIF overexpression significantly attenuated cisplatin-or paclitaxel-induced apoptosis of the endometrial cancer cells (P < 0.05) and markedly increased mitochondrial membrane potential of the cells (P < 0.05). The expressions of Bcl-2, Bcl-xL and p-STAT3 proteins increased obviously while the expressions of Bax, Bad and STAT3 either decreased or showed no obvious changes in the LIF-overexpressing cells. Overexpressing LIF significantly enhanced the transcriptional activity of STAT3 (P < 0.05), and silencing STAT3 obviously enhanced apoptosis of the endometrial cancer cells overexpressing LIF (P < 0.05). CONCLUSIONS: s Overexpression of LIF can enhance cisplatin and paclitaxel resistance to endometrial cancer cells in vitro.
Authors: Quanwen Li; Erica Louden; Jordan Zhou; Sascha Drewlo; Jing Dai; Elizabeth E Puscheck; Kang Chen; Daniel A Rappolee Journal: Stem Cells Dev Date: 2019-01-07 Impact factor: 3.272
Authors: Xin Zhang; Dong Ren; Ling Guo; Lan Wang; Shu Wu; Chuyong Lin; Liping Ye; Jinrong Zhu; Jun Li; Libing Song; Huanxin Lin; Zhenyu He Journal: Breast Cancer Res Date: 2017-02-08 Impact factor: 6.466
Authors: Amy M Buckley; Niamh Lynam-Lennon; Susan A Kennedy; Margaret R Dunne; John J Aird; Emma K Foley; Niamh Clarke; Narayanasamy Ravi; Dermot O'Toole; John V Reynolds; Breandán N Kennedy; Jacintha O'Sullivan Journal: Oncotarget Date: 2018-09-14