AIM: Metformin plays an important role in the inhibition of cancer cell growth and prolongs remission durations. It reverses progestin-resistance in endometrial cancer cells by downregulating glyoxalase I (GloI) expression. This study aimed to investigate the effect of metformin on endometrial cancer cell chemotherapeutic sensitivity and explore the underlying molecular mechanisms. MATERIAL AND METHODS: MTT assay was performed to determine the rate of cell death after cisplatin and paclitaxel with or without metformin. Western blot was carried out to analyze GloI expression. SiRNA-targeting of GloI was used to knockdown GloI expression before further treatment with chemotherapeutic agents to examine the effect of GloI downregulation on chemotherapy-induced cell killing. In addition, plasmid transfection was used to overexpress GloI and determine whether high GloI levels blocked metformin-enhanced cell sensitivity to chemotherapy. PCR was used to analyze the efficiency of RNA interference and plasmid transfection. RESULTS: The addition of metformin enhanced the sensitivity of endometrial cells to cisplatin and paclitaxel, which was associated with reduced levels of GloI expression. Moreover, low-dose chemotherapeutic drugs alone could not significantly reduce GloI expression, whereas the addition of metformin potently downregulated GloI protein levels. Cisplatin and paclitaxel markedly inhibited the proliferative ability of GloI-depleted endometrial cancer cells. However, the overexpression of GloI abolished the effect of metformin-enhanced cell sensitivity to chemotherapeutic drugs. CONCLUSION: Metformin enhances the rate of cell-killing induced by chemotherapeutic agents by repressing GloI expression.
AIM: Metformin plays an important role in the inhibition of cancer cell growth and prolongs remission durations. It reverses progestin-resistance in endometrial cancer cells by downregulating glyoxalase I (GloI) expression. This study aimed to investigate the effect of metformin on endometrial cancer cell chemotherapeutic sensitivity and explore the underlying molecular mechanisms. MATERIAL AND METHODS:MTT assay was performed to determine the rate of cell death after cisplatin and paclitaxel with or without metformin. Western blot was carried out to analyze GloI expression. SiRNA-targeting of GloI was used to knockdown GloI expression before further treatment with chemotherapeutic agents to examine the effect of GloI downregulation on chemotherapy-induced cell killing. In addition, plasmid transfection was used to overexpress GloI and determine whether high GloI levels blocked metformin-enhanced cell sensitivity to chemotherapy. PCR was used to analyze the efficiency of RNA interference and plasmid transfection. RESULTS: The addition of metformin enhanced the sensitivity of endometrial cells to cisplatin and paclitaxel, which was associated with reduced levels of GloI expression. Moreover, low-dose chemotherapeutic drugs alone could not significantly reduce GloI expression, whereas the addition of metformin potently downregulated GloI protein levels. Cisplatin and paclitaxel markedly inhibited the proliferative ability of GloI-depleted endometrial cancer cells. However, the overexpression of GloI abolished the effect of metformin-enhanced cell sensitivity to chemotherapeutic drugs. CONCLUSION:Metformin enhances the rate of cell-killing induced by chemotherapeutic agents by repressing GloI expression.
Authors: Hui Guo; Weimin Kong; Lu Zhang; Jianjun Han; Leslie H Clark; Yajie Yin; Ziwei Fang; Wenchuan Sun; Jiandong Wang; Timothy P Gilliam; Douglas Lee; Liza Makowski; Chunxiao Zhou; Victoria L Bae-Jump Journal: Am J Cancer Res Date: 2019-10-01 Impact factor: 6.166
Authors: Nicole S Nevadunsky; Anne Van Arsdale; Howard D Strickler; Alyson Moadel; Gurpreet Kaur; Marina Frimer; Erin Conroy; Gary L Goldberg; Mark H Einstein Journal: Gynecol Oncol Date: 2013-11-02 Impact factor: 5.482
Authors: Tajudeen Olabisi Obafemi; Oluwaseun R Olasehinde; Oyindamola A Olaoye; Kikelomo F Jaiyesimi; Funmilayo D Adewumi; Olusola B Adewale; Blessing A Afolabi Journal: J Diabetes Metab Disord Date: 2020-05-16
Authors: Rive Sarfstein; Yael Friedman; Zohar Attias-Geva; Ami Fishman; Ilan Bruchim; Haim Werner Journal: PLoS One Date: 2013-04-19 Impact factor: 3.240