Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (4): 35-41.doi: 10.6040/j.issn.1671-7554.0.2020.1753

Previous Articles     Next Articles

Effects of curcumin on progesterone resistance in endometrial carcinoma

DING Fei, JIANG Jie   

  1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2021-04-30

PDF (PC)

206

Abstract: Objective To explore the effects of different concentrations of curcumin on progesterone resistant cells in endometrial carcinoma and to investigate the role of related signaling pathways influencing progesterone resistance. Methods The target genes of curcumin were analyzed in the ETCM and GEPIA databases and the interaction genes related to tumor-drug resistance were screened out. The resistance of an established progesterone-resistance model of Ishikawa cells in endometrial carcinoma(IshikawaPR cell line)was detected. Resistant cells were divided into curcumin(0, 5, 10, 20, 40, 60, 80 μmoL)groups, progesterone(0, 5, 10, 20, 40, 60, 90 μmoL)groups and curcumin+progesterone(the same concentration)groups, according to different treatments. The proliferation of cells in each group was determined with MTT. The effects of curcumin on the resistant cells were assessed with EDU, Transwell and mitochondrial membrane potential. The changes of intracellular protein levels after curcumin stimulation at different concentrations were determined with Western blotting. The potential signaling pathways were analyzed in the databases. Results Analyses of the databases indicated that curcumin target genes were closely related to tumor-drug resistance genes such as PGR and ESR. MTT results showed that curcumin inhibited the growth of drug-resistant cells, leading to a decrease in cell survival rate(F=907.8, P<0.001), and there was an interactive relationship between curcumin and progesterone(F=51.34, P=0.004). When the concentrations of progesterone were 10 μmoL(t=16.13, P=0.026), 20 μmoL(t=33.23, P=0.006), and 40μmoL(t=35.94, P=0.005), combination with curcumin inhibited drug-resistant cells more effectively than the use of progesterone alone. Curcumin treatment(0, 10, 20 μmoL)inhibited the proliferation(F=205.8, P<0.001), invasion(F=13.9, P=0.006)and promoted apoptosis(F=23.3, P=0.002)of drug-resistant cells. Western blotting showed that after curcumin treatment, the levels of CyclinD1, CASP3, MMP2 and p-NFκB decreased while the level of PR increased in resistant cells. Conclusion Curcumin inhibits progesterone resistance in endometrial carcinoma, possibly by mediating inactivation of transcription factor NFκB.

Key words: Curcumin, Endometrial carcinoma, Progesterone, Resistance, Nuclear transcription factor-κB

CLC Number: 

  • R711
[1] 吴彧, 夏彦清, 伍玥, 等. 炎性细胞模型中姜黄素对胆固醇逆转运蛋白ABCA1和ABCG1基因的影响 [J]. 山东大学学报(医学版), 2016, 54(11): 24-26. WU Song, XIA Yanqing, WU Yue, et al. Effect of curcumin on ABCA1 and ABCG1 genes in an inflammatory cell model [J]. Journal of Shandong University(Health Sciences), 2016, 54(11): 24-26.
[2] Hosseini-Zare M S, Sarhadi M, Zarei M, et al. Synergistic effects of curcumin and its analogs with other bioactive compounds: A comprehensive review [J]. Eur J Med Chem, 2021, 210: 113072. doi: 10.1016/j.ejmech.2020.113072.
[3] Mukherjee S, Baidoo J N E, Fried A, et al. Using curcumin to turn the innate immune system against cancer [J]. Biochem Pharmacol, 2020, 176: 113824. doi: 10.1016/j.bcp.2020.113824.
[4] Gentry-Maharaj A, Karpinskyj C. Current and future approaches to screening for endometrial cancer [J]. Best Pract Res Clin Obstet Gynaecol, 2020, 65:79-97.
[5] 沈偲, 滕银成. 子宫内膜癌孕激素耐药机制及新型疗法的研究进展[J]. 上海交通大学学报(医学版), 2020, 40(12): 1677-1682. SHEN Cai, TENG Yincheng. Research progress on the mechanism of progesterone resistance and novel therapy in endometrial carcinoma [J]. Journal of Shanghai Jiaotong University(Health Sciences), 2020, 40(12): 1677-1682.
[6] Zhou Q, Li W, Kong D, et al. DACH1 suppresses epithelial to mesenchymal transition(EMT)through Notch1 pathway and reverses progestin resistance in endometrial carcinoma [J]. Cancer Med, 2019, 8(9): 4380-4388.
[7] Ozawa-umeta H, Kishimoto A, Imaizumi A, et al. Curcumin β-D-glucuronide exhibits anti-tumor effects on oxaliplatin-resistant colon cancer with less toxicity in vivo [J]. Cancer Sci, 2020, 111(5): 1785-1793.
[8] Zeng Y, Du Q, Zhang Z, et al. Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress [J]. Arch Biochem Biophys, 2020, 694: 108613. doi: 10.1016/j.abb.2020.108613
[9] Li W, Sun L, Lei J, et al. Curcumin inhibits pancreatic cancer cell invasion and EMT by interfering with tumor-stromal crosstalk under hypoxic conditions via the IL-6/ERK/NF-κB axis [J]. Oncol Rep, 2020, 44(1): 382-392.
[10] Liczbinski P, Michalowicz J, Bukowska B. Molecular mechanism of curcumin action in signaling pathways: Review of the latest research [J]. Phytother Res, 2020, 34(8): 1992-2005.
[11] Patel SS, Acharya A, Ray RS, et al. Cellular and molecular mechanisms of curcumin in prevention and treatment of disease [J]. Crit Rev Food Sci Nutr, 2020, 60(6): 887-939.
[12] Barzegar A, Moosavi-Movahedi AA. Intracellular ROS protection efficiency and free radical-scavenging activity of curcumin [J]. PLoS One, 2011, 6(10): e26012.
[13] Fathy Abd-Ellatef GE, Gazzano E, Chirio D, et al. Curcumin-loaded solid lipid Nanoparticles bypass P-Glycoprotein mediated doxorubicin resistance in triple negative breast cancer cells [J]. Pharmaceutics, 2020, 12(2):96. doi: 10.3390/pharmaceutics12020096.
[14] Chen P, Huang HP, Wang Y, et al. Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death [J]. J Exp Clin Cancer Res, 2019, 38(1): 254. doi: 10.1186/s13046-019-1234-8.
[15] Ashrafizadeh M, Zarrabi A, Hashemi F, et al. Curcumin in cancer therapy: a novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects [J]. Life Sci, 2020, 256:117984. doi: 10.1016/j.lfs.2020.117984.
[16] He B, Wei W, Liu J, et al. Synergistic anticancer effect of curcumin and chemotherapy regimen FP in human gastric cancer MGC-803 cells [J]. Oncol Lett, 2017, 14(3): 3387-3394.
[17] Yoshida K, Toden S, Ravindranathan P, et al. Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression [J]. Carcinogenesis, 2017, 38(10): 1036-1046.
[18] Papiez MA, Krzysciak W, Szade K, et al. Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species [J]. Drug Des Devel Ther, 2016, 10:557-570. doi: 10.2147/DDDT.S92687.eCollection 2016.
[19] Keyvani-Ghamsari S, Khorsandi K, Gul A. Curcumin effect on cancer cells multidrug resistance: An update [J]. Phytother Res, 2020, 34(10): 2534-2556.
[20] Bi M, Zhang Z, Jiang YZ, et al. Enhancer reprogramming driven by high-order assemblies of transcription factors promotes phenotypic plasticity and breast cancer endocrine resistance [J]. Nat Cell Biol, 2020, 22(6): 701-715.
[21] Cai H, Yan L, Liu N, et al. IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway [J]. Biomed Pharmacother, 2020, 123: 109790. doi: 10.1016/j.biopha.2020.110077.
[22] Vergani E, Dugo M, Cossa M, et al. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators [J]. Cell Commun Signal, 2020, 18(1): 156. doi: 10.1186/s12964-020-00601-1.
[23] Xing Y, Yan J, Niu Y. PXR: a center of transcriptional regulation in cancer [J]. Acta Pharm Sin B, 2020, 10(2): 197-206.
[24] Westerouen Van Meeteren MJ, Drenth JPH, Tjwa ETTL. Elafibranor: a potential drug for the treatment of nonalcoholic steatohepatitis(NASH)[J]. Expert Opin Investig Drugs, 2020, 29(2): 117-123.
[25] Toporova L, Balaguer P. Nuclear receptors are the major targets of endocrine disrupting chemicals [J]. Mol Cell Endocrinol, 2020, 502: 110665. doi: 10.1016/j.mce.2019.110665.
[26] 崔明花, 付二花, 林贞花, 等. 姜黄素抗肿瘤药理作用的研究进展[J]. 中国临床药理学杂志, 2021, 37(2): 186-188. CUI Minghua, FU Erhua, LIN Zhenhua, et al. Research progress of antitumor pharmacological effects of curcumin [J]. The Chinese Journal of Clinical Pharmacology, 2021, 37(2): 186-188.
[1] ZHANG Yuan, LI Yang-Min, FENG Rue-Qiu, CHANG Cai-Yun, PAN Hua-Wei, WANG Shu-Mei. Relationship among serum adiponectin level, obesity and insulin resistance [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 124-.
[2] GE Li-Juan, JIN Rui-Feng, WANG Ji-Wen, HU Xin-Sheng, LIKun. Association between the C1236T polymorphism in multi-drug resistance gene 1 and response to antiepileptic drug treatment in epileptic patients [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 99-102.
[3] ZHAO Ge, ZOU Cunhua, SONG Dongdong, ZHAO Shuping. Effects of tanshinone IIA on the proliferation and apoptosis of endometrial carcinoma cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 53-58.
[4] LIU Teng, MA Yingchun. Expression of ECT2 in uterine corpus endometrial carcinoma and its clinical significance based on bioinformatics database [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 63-71.
[5] LI Yan, LIU Jing, LI Juan, YANG Qiuhong. Clinical characteristics and placental pathology of bloodstream infection in 50 pregnant women [J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 48-54.
[6] Jianhua JU,Zhenye YANG,Qinglian LI,Ya'nan HAN,Yanqing LI,Yijun QIAO,Hu YANG,Huaran ZHANG. Advances on drugs derived from microbial sources and future perspectives [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 43-50,63.
[7] Zhuxiu CHU,Wenjing ZHAO,Xiaoyan LI,Xiaoli KONG,Tingting MA,Liyu JIANG,Qifeng YANG. Significance of neoadjuvant chemotherapy and molecular marker changes in 218 women with breast cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 130-139.
[8] Chunfang HA,Ruyue LI. Research progress of drug resistance in ovarian cancer and targeted therapy strategy [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 117-123.
[9] NIU Qun, SHI Jingjing, FU Jiang. Effects of WNT5A gene on insulin reactivity and insulin resistance in granulosa cells [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 57-63.
[10] XU Bing, LI Yong, LIU Ming, LIU Yonghui. Silencing PRRX1 gene expression enhances the sensitivity of prostate cancer resistant cell line PC-3/DTX to docetaxel [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 103-110.
[11] HA Lingxia, YIN Ting, WU Yangyang, LI Weixia, DU Yudong. Correlation between insulin resistance and expressions of local inflammatory factors and glucose transporter protein type-4 in the endometrium of patients with polycystic ovary syndrome [J]. Journal of Shandong University (Health Sciences), 2021, 59(11): 41-47.
[12] ZHAO Lihong, ZHAO Shuping, NIE Shenggang, SUN Jing, JIANG Tongfeng. Distribution and antimicrobial resistance of multiple pathogens in 507 males with genital tract infections [J]. Journal of Shandong University (Health Sciences), 2021, 59(1): 55-58.
[13] XIONG Yixuan, ZHAO Bin, JIA Linglu, ZHANG Wenjing, XU Xin. Curcumin upregulates osteogenesis under inflammatory condition in periodontal ligament stem cells via Nrf2 signaling pathway [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 19-26.
[14] XU Hongzhao, HAO Zongshan, SHEN Deqiang, LI Zhaoping, CHEN Liyong. Ribosomal protein S6 kinase 2 silencing in ethanol-induced myocardial insulin resistance [J]. Journal of Shandong University (Health Sciences), 2020, 58(4): 84-89.
[15] SUN Yanting, WU Dawei, WANG Xiaofei, XU Jian, WANG Rui. Distribution and drug resistance change of clinical isolates in ICU of a new hospital [J]. Journal of Shandong University (Health Sciences), 2020, 58(2): 64-71.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] JIANG Bao-dong,MA Xiang-xing,WANG Qing,WANG Qian,FENG Xiao-yuan,LI Ke,YU Fu-hua. Imaging parameters of multislice spiral CT venography in cerebral veins[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1084 -1086 .
[2] TANG Fang1,2, ZHANG Yingqian3, WANG Zhiqiang4, KANG Dianmin4,
WANG Jiezhen1, XUE Fuzhong1. A 2D minimal spanning tree model of the spatial structures of natural focal disease[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(01): 106 -110 .
[3] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
[4] SHAO Haigang, WANG Xuan, WANG Qing. Anatomy of the root canal system of mandibular first premolar in population of Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 85 -89 .
[5] ZHU Xiaoli1, GUO Shuling1, SU Lei1, FENG Yuxin2, YUAN Fangshu1. Extraction of total proteins from demodex and qualification of their molecular weights[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(5): 58 -62 .
[6] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[7] ZHONG Nv-juan1, SONG Yong-mei2, LIU Gengsheng2, XUE Fu-zhong1, LIU Yan-xun1. Construction and application of the Bayes network model in
traditional Chinese medicine elements[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(2): 157 .
[8] LIU Hai-Chun, ZHANG Jian-Feng, CHEN Yuan-zhen. Bone collagen and biomechanical propertyies in the femur of osteoporosis rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(5): 42 -45 .
[9] FENG Fuli1, WEI Shuzhen2, ZHANG Yonghuan3, LI Li1, CHEN Rong1, LIRuifeng1. Relationship between high mortality and altered expression of Klotho in insulin resistance rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(6): 5 -8 .
[10] LI Yu-liang,WANG Yong-zheng,WANG Xiao-hua,ZHANG Fu-jun,ZHU Li-dong,ZHANG Wang-ming,LI Zheng,LI Zhen-jia,ZHANG Kai-xian. I implantation combined with Gemcitabine in the treatment of advanced pancreatic cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(4): 393 -396 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd