β-榄香烯对人乳头状甲状腺癌细胞生物学行为的影响及其作用机制
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摘要
目的:研究β-榄香烯对人乳头状甲状腺癌(PTC)的治疗作用并探讨其作用机制。方法:选择人PTC中TPC-1、K1细胞系为研究对象,以不同浓度β-榄香烯分别作用于两个细胞系。采用CCK-8比色法分析细胞增殖情况;流式细胞仪检测对细胞凋亡和周期的影响;Transwell小室法观察细胞侵袭性的变化。结果:经β-榄香烯处理后,TPC-1和K1细胞增殖被抑制,且呈时间-浓度依赖性。当β-榄香烯浓度分别为40、60μg/ml时,TPC-1细胞凋亡比例升高,且差异有统计学意义(P<0.05);当β-榄香烯浓度分别为20、40μg/ml时,K1细胞凋亡比例升高,且差异有统计学意义(P<0.05)。当β-榄香烯浓度为60μg/ml时,TPC-1细胞在G_1期所占比例显著增高(P<0.05);当β-榄香烯浓度为10、20和40μg/ml时K1细胞在G_2/M期所占比例显著增高(P<0.05)。经β-榄香烯处理后,TPC-1、K1细胞穿过基质胶的细胞数均明显减少(P<0.05)。结论:β-榄香烯对PTC有抗肿瘤作用,有潜力成为治疗PTC的一种化疗药物。
Objective:To investigate the therapeutic effect of β-elemene on human papillary thyroid cancer(PTC).Methods:TPC-1 and K1 cell lines were dealt with different concentrations of β-elemene to observe its effects on the tumor's biological characteristics.CCK-8 was used to analyze the proliferative capacity.Flow cytometry was used to detect the apoptosis and cell cycles.Transwell was used to investigate the tumor's invasive ability.Results:The proliferation ability of TPC-1 and K1 cells was limited in a time-concentration-dependent way after the treatment of β-elemene.The apoptosis ratio of TPC-1 cell was statistically higher than the control group(P<0.05) while disposed to 40 and 60 μg/ml β-elemene.The apoptosis ratio of K1 was statistically higher than the control group(P<0.05) while disposed to 20 and 40 μg/ml β-elemene.TPC-1 cells were in a statistically higher proportion of G_1 phase(P<0.05) while disposed to 60 μg/ml β-elemene.When disposed to 10,20 and 40μg/ml β-elemene,statistically more K1 cells were blocked in G_2/M phase(P<0.05).After treated with β-elemene,statistically less TPC-1 and K1 cells went through the matrigel(P<0.05).Conclusion:β-elemene has a remarkable antitumor effect on PTC cells.It could be a promising chemotherapy drug for PTC.
Objective:To investigate the therapeutic effect of β-elemene on human papillary thyroid cancer(PTC).Methods:TPC-1 and K1 cell lines were dealt with different concentrations of β-elemene to observe its effects on the tumor's biological characteristics.CCK-8 was used to analyze the proliferative capacity.Flow cytometry was used to detect the apoptosis and cell cycles.Transwell was used to investigate the tumor's invasive ability.Results:The proliferation ability of TPC-1 and K1 cells was limited in a time-concentration-dependent way after the treatment of β-elemene.The apoptosis ratio of TPC-1 cell was statistically higher than the control group(P<0.05) while disposed to 40 and 60 μg/ml β-elemene.The apoptosis ratio of K1 was statistically higher than the control group(P<0.05) while disposed to 20 and 40 μg/ml β-elemene.TPC-1 cells were in a statistically higher proportion of G_1 phase(P<0.05) while disposed to 60 μg/ml β-elemene.When disposed to 10,20 and 40μg/ml β-elemene,statistically more K1 cells were blocked in G_2/M phase(P<0.05).After treated with β-elemene,statistically less TPC-1 and K1 cells went through the matrigel(P<0.05).Conclusion:β-elemene has a remarkable antitumor effect on PTC cells.It could be a promising chemotherapy drug for PTC.
引文
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[2] Wang Z,Li Y,Zhou F,et al.Beta-elemene enhances anticancer bone neoplasms efficacy of paclitaxel through regulation of GPR124 in bone neoplasms cells[J].Oncol Lett,2018,16(2):2143-2150.
[3] Xu L,Guo T,Qu X,et al.Beta-elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts[J].Cell Biol Int,2018,42(10):1377-1385.
[4] Guo Z,Liu Z,Yue H,et al.Beta-elemene increases chemosensitivity to 5-fluorouracil through down-regulating microRNA-191 expression in colorectal carcinoma cells[J].J Cell Biochem,2018,119(8):7032-7039.
[5] Wang L,Zhao Y,Wu Q,et al.Therapeutic effects of beta-elemene via attenuation of the Wnt/beta-catenin signaling pathway in cervical cancer cells[J].Mol Med Rep,2018,17(3):4299-4306.
[6] Liu Y,Jiang ZY,Zhou YL,et al.Beta-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1alpha/ATF6 pathway[J].Biomed Pharmacother,2017,93:490-497.
[7] Li X,Lin Z,Zhang B,et al.Beta-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1[J].Sci Rep,2016,6:21010.
[8] Jiang Z,Jacob JA,Loganathachetti DS,et al.Beta-elemene:Mechanistic studies on cancer cell interaction and its chemosensitization effect[J].Front Pharmacol,2017,8:105.
[9] Li X,Zhou Y,Chen L.The main antitumor mechanism and the research progress in non-neoplastic diseases of β-elemene[J].Anhui Med Pharm,2015,19(8):1429-1432.[李雪,周赟,陈蕾.β-榄香烯主要抗肿瘤机制及在非肿瘤性疾病中的研究进展[J].安徽医药,2015,19(8):1429-1432.]
[10] Ahn HS,Kim HJ,Welch HG.Korea's thyroid-cancer "epidemic"-screening and overdiagnosis[J].N Engl J Med,2014,371(19):1765-1767.
[11] Davies L,Welch HG.Current thyroid cancer trends in the united states[J].JAMA Otolaryngol Head Neck Surg,2014,140(4):317-322.
[12] Wang Ximing,Hu Xuejun.Research progress on the anti-tumor mechanism and reversal mechanism of drug resistance of β-elemene[J].Modern Oncology,2014,22(7):1711-1714.[王希明,胡雪君.β-榄香烯抗肿瘤及逆转耐药机制的研究进展[J].现代肿瘤医学,2014,22(7):1711-1714.]
[13] Li CL,Chang L,Guo L,et al.Beta-elemene induces caspase-dependent apoptosis in human glioma cells in vitro through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2[J].Asian Pac J Cancer Prev,2014,15(23):10407-10412.
[14] Li QQ,Wang G,Huang F,et al.Sensitization of lung cancer cells to cisplatin by beta-elemene is mediated through blockade of cell cycle progression:Antitumor efficacies of beta-elemene and its synthetic analogs[J].Med Oncol,2013,30(1):488.
[15] Wu B,Jiang Y,Zhu F,et al.Demethylation effects of elemene on the GSTP1 gene in HCC cell line QGY7703[J].Oncol Lett,2016,11(4):2545-2551.
[16] Shi H,Liu L,Liu L,et al.Beta-elemene inhibits the metastasis of B16F10 melanoma cells by downregulation of the expression of uPA,uPAR,MMP-2,and MMP-9[J].Melanoma Res,2014,24(2):99-107.
[17] Chen W,Lu Y,Wu J,et al.Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis[J].Cancer Chemother Pharmacol,2011,67(4):799-808.
[18] Li LJ,Zhong LF,Jiang LP,et al.β-elemene radiosensitizes lung cancer A549 cells by enhancing DNA damage and inhibiting DNA repair[J].Phytother Res,2011,25:1095-1097.
[19] Liu JS,Che XM,Chang S,et al.β-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation[J].World J Gastroenterol,2015,21(34):9945-9956.
[20] Shi XG,Gao Y,Teng WP.The inhibition of β-elemene in thyroid cancer cells and the mechanism research in vitro[J].Chin J Pract Int Med,2009,29(6):557-558.[史晓光,高芸,滕卫平.β-榄香烯抑制甲状腺癌细胞增殖及其作用机制体外实验研究[J].中国实用内科杂志,2009,29(6):557-558.]