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

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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

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.
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