丹参酮IIA对子宫内膜癌细胞增殖与凋亡的影响

doi:10.6040/j.issn.1671-7554.0.2021.1471

摘要/Abstract

摘要： 目的探讨丹参酮IIA对子宫内膜癌细胞增殖与凋亡的影响。方法将丹参酮IIA作用后的子宫内膜癌细胞设置为对照组、低浓度组(1 μg/mL)、中浓度组(2.5 μg/mL)及高浓度组(5 μg/mL);同时将酪蛋白激酶2(CK2)特异性磷酸化抑制剂(TBB)和丹参酮IIA共同处理后的细胞设置为对照组、TBB组(60 μmol)、药物组(5 μg/mL)及药物(5 μg/mL)+TBB组(60 μmol)。结晶紫染色法检测丹参酮IIA对子宫内膜癌细胞增殖的影响;Western blotting检测各组子宫内膜癌细胞中P53、活化胱天蛋白酶-3(Cleaved caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)、CK2α、乳腺癌缺失因子1(DBC1)、沉默信息调节因子1(SIRT1)、磷酸化乳腺癌缺失因子1(p-DBC1)的表达;同时加入TBB,检测子宫内膜癌细胞中CK2α、DBC1、p-DBC1的表达。结果结晶紫染色结果显示,对照组和高浓度组各时间点(24、48、72 h)细胞增殖率分别为(0.87±0.05)%、(0.61±0.04)%、(0.30±0.04)%、(0.09±0.04)%,差异有统计学意义(F=217.976,P<0.001)。Western blotting结果显示,在丹参酮IIA作用下,P53(F=244.261)及Cleaved caspase-3(F=290.842)的表达水平呈浓度依赖性升高,Bcl-2(F=198.170)的表达水平呈浓度依赖性降低,差异均有统计学意义(P均<0.001);p-DBC1/DBC1的表达水平呈浓度依赖性降低,差异有统计学意义(F=187.092, P<0.001),而CK2α、SIRT1的表达差异均无统计学意义(P均>0.05);单独应用TBB(F=7.847)、丹参酮IIA(F=827.715)及联合应用(F=22.174),p-DBC1/DBC1表达均受到抑制,与对照组比较,差异均有统计学意义(P=0.023,P<0.001,P=0.002);CK2α表达差异无统计学意义(P>0.05)。结论丹参酮IIA可以明显抑制子宫内膜癌细胞增殖并诱导凋亡,其机制可能与CK2/DBC1/SIRT1/P53信号通路有关。

关键词: 丹参酮IIA, 子宫内膜癌, 细胞凋亡, 细胞增殖, 磷酸化

Abstract: Objective To investigate the effects of tanshinone IIA on the proliferation and apoptosis of endometrial carcinoma cells. Methods According to the experimental requirements, endometrial carcinoma cells treated with tanshinone IIA were divided into the control group, low concentration group(1 μg/mL), medium concentration group(2.5 μg/mL)and high concentration group(5 μg/mL). Meanwhile, cells co-treated with CK2 specific phosphorylation inhibitor(TBB)and tanshinone IIA were divided into the control group, TBB group(60 μmol), drug group(5 μg/mL)and drug(5 μg/mL)+ TBB group(60 μmol). The effects of tanshinone IIA on the proliferation of cells were detected with crystal violet staining; expressions of P53, Cleaved caspase-3, B-cell lymphoma-2(Bcl-2), casein kinase 2α(CK2α), deletion in breast cancer 1(DBC1), silent information regulator 1(SIRT1)and p-deletion in breast cancer 1(p-DBC1)were detected with Western blotting. After TBB was added, expressions of CK2α, DBC1 and p-DBC1 were also detected. Results The results of crystal violet staining showed that the proliferation rates of the control group and high concentration group at each time point(24 h, 48 h, 72 h)were(0.87±0.05)%,(0.61±0.04)%,(0.30±0.04)% and(0.09±0.04)%, respectively(F=217.976, P<0.001). The results of Western blotting showed that under the action of tanshinone IIA, the expressions of P53(F=244.261)and Cleaved caspase-3(F=290.842)increased in a concentration-dependent manner, while the expression of Bcl-2(F=198.170)decreased in a concentration-dependent manner(P<0.001), and the expression of p-DBC1/DBC1 decreased in a concentration-dependent manner(F=187.092, P<0.001), but there was no significant difference in CK2α and SIRT1 expressions(P>0.05). The expression of p-DBC1/DBC1 was inhibited by TBB(F=7.847), tanshinone IIA(F=827.715)and their combination(F=22.174), and the difference was statistically significant compared with the control group(P=0.023,P<0.001, P=0.002), but there was no significant difference in CK2α expression(P>0.05). Conclusion Tanshinone IIA can significantly inhibit the proliferation and induce apoptosis of endometrial carcinoma cells, and the mechanism may be related to the CK2/DBC1/SIRT1/P53 signaling pathway.

Key words: Tanshinone IIA, Endometrial carcinoma, Apoptosis, Cell proliferation, Phosphorylation

中图分类号:

R737.33

赵舸,邹存华,宋冬冬,赵淑萍. 丹参酮IIA对子宫内膜癌细胞增殖与凋亡的影响[J]. 山东大学学报 (医学版), 2022, 60(9): 53-58.

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.

参考文献

[1] Urick ME, Bell DW. Clinical actionability of molecular targets in endometrial cancer[J]. Nat Rev Cancer, 2019, 19(9): 510-521.
[2] 魏静, 张为远. 早期子宫内膜癌患者药物治疗中存在的问题[J]. 中国妇产科临床杂志, 2019, 20(1): 87-89. WEI Jing, ZHANG Weiyuan. Problems in drug treatment of patients with early endometrial cancer[J]. Chinese Journal of Obstetrics and Gynecology, 2019, 20(1): 87-89.
[3] Wortman BG, Nout RA, Bosse T, et al. Selecting adjuvant treatment for endometrial carcinoma using molecular risk factors[J]. Curr Oncol Rep, 2019, 21(9): 83. doi: 10.1007/s11912-019-0825-z.
[4] Zhou M, Zhou G, Hu SH, et al. Tanshinone IIA suppress the proliferation of HNE-1 nasopharyngeal carcinoma an in vitro study[J]. Saudi J Biol Sci, 2018, 25(2): 267-272.
[5] International BMR. Retracted: tanshinone IIA induces apoptosis in human oral cancer KB cells through a mitochondria-dependent pathway[J]. Biomed Res Int, 2017: 9496485. doi: 101155/2017/9496485.
[6] Jeon YJ, Kim JS, Hwang GH, et al. Inhibition of cytochrome P4502J2 by tanshinone IIA induces apoptotic cell death in hepatocellular carcinoma HepG2 cells[J]. Eur J Pharmacol, 2015, 764: 480-488. doi: 10.1016/j.ejphar.2015.07.047.
[7] Lin JY, Ke YM, Lai JS, et al. Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells[J]. Phytomedicine, 2015, 22(10): 929-938.
[8] Lin H, Zheng L, Li S, et al. Cytotoxicity of tanshinone IIA combined with taxol on drug-resist breast cancer cells MCF-7 through inhibition of tau[J]. Phytother Res, 2018, 32(4): 1-5.
[9] Dong W, Zhang Y, Chen X, et al. High-dose tanshinone IIA suppresses migration and proliferation while promoting apoptosis of astrocytoma cells via notch-1 pathway[J]. Neurochem Res, 2018, 43(9): 1855-1861.
[10] Su CC. Tanshinone IIA inhibits gastric carcinoma AGS cells by decreasing the protein expression of VEGFR and blocking Ras/Raf/MEK/ERK pathway[J]. Int J Mol Med, 2018, 41(4): 2389-2396.
[11] 鲁强, 管东方, 吴艳丽, 等. 靶向调控SIRT1基因表达对子宫内膜癌细胞生物学行为的影响及其机制研究[J]. 中国妇产科临床杂志, 2021, 22(3): 261-263. LU Qiang, GUAN Dongfang, WU Yanli, et al. Effect of targeting SIRT1 gene expression on biological behavior of endometrial cancer cells and its mechanism[J]. Chinese Journal of Obstetrics and Gynecology, 2021, 22(3): 261-263.
[12] Genestie C, Leary A, Devouassoux M, et al. Histological and molecular classification of endometrial carcinoma and therapeutical implications[J]. Bull Cancer, 2017, 104(12): 1001-1012.
[13] Psilopatis I, Pergaris A, Giaginis C, et al. Histone deacetylase inhibitors: a promising therapeutic alternative for endometrial carcinoma[J]. Dis Markers, 2021: 7850688. doi: 10.1155/2021/7850688.
[14] Huvila J, Pors J, Thompson EF, et al. Endometrial carcinoma: molecular subtypes, precursors and the role of pathology in early diagnosis[J]. J Pathol, 2021, 253(4): 355-365.
[15] Lee YT, Tan YJ, Oon CE. Molecular targeted therapy: Treating cancer with specificity[J]. Eur J Pharmacol, 2018, 834: 188-196. doi: 10.1016/j.ejphar.2018.07.034.
[16] Wang Z, Meng F, Zhong Z. Emerging targeted drug delivery strategies toward ovarian cancer[J]. Adv Drug Deliv Rev, 2021, 178: 113969. doi: 10.1016/j.addr.2021.113969.
[17] Fang ZY, Zhang M, Liu JN, et al. Tanshinone IIA: a review of its anticancer effects[J]. Front Pharmacol, 2021, 11: 611087. doi: 10.3389/fphar.2020.611087.
[18] Jalal T, Natto HA, Wahab RA. Cytotoxicity and toxicological studies of artocarpus altilis extracts, inducing apoptosis and cell cycle arrest via caspase-3 and caspase-8 pathways against human breast MCF-7 cells[J]. Comb Chem High Throughput Screen, 2022, 25(6): 973-985.
[19] Ghaffari K, Ahmadi R, Saberi B, et al. Anti-proliferative effects of Ziziphus spina-christi and Phlomis russeliana leaf extracts on HEK293 and MCF-7 Cell Lines and Evaluation of Bax and Bcl-2 Genes Expression Level in MCF-7 Cells[J]. Asian Pac J Cancer Prev, 2021, 22(S1): 81-87.
[20] Li W, Li F, Zhang X, et al. Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment[J]. Signal Transduct Target Ther, 2021, 6(1): 422. doi: 10.1038/s41392-021-00825-8.
[21] Fang Q, Bellanti JA, Zheng SG. Advances on the role of the deleted in breast cancer(DBC1)in cancer and autoimmune diseases[J]. J Leukocyte Biol, 2021, 109(2): 449-454.
[22] Brandl L, Zhang Y, Kirstein N, et al. Targeting c-MYC through interference with NAMPT and SIRT1 and their association to oncogenic drivers in murine serrated intestinal tumorigenesis[J]. Neoplasia, 2019, 21(10): 974-988.
[23] Yin CF, Kao SC, Hsu CL, et al. Phosphoproteome analysis reveals dynamic heat shock protein 27 phosphorylation in tanshinone IIA-induced cell death[J]. J Proteome Res, 2020, 19(4): 1620-1634.
[24] Tang S, Yuan Y, Liu Z, et al. Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis[J]. Biochem Biophys Res Commun, 2020, 530(4): 686-691.
[25] Li L, Feng R, Fei S, et al. NANOGP8 expression regulates gastric cancer cell progression by transactivating DBC1 in gastric cancer MKN-45 cells[J]. Oncol Lett, 2019, 17(1): 555-563.
[26] Jung M, Park KH, Kim HM, et al. Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer[J]. Gastric Cancer, 2019, 22(6):1153-1163.

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