Effect and mechanism of oleanolic acid on proliferation and apoptosis of lung adenocarcinoma A549 cells
LI Kairui1 LIU Jie1 LI Xiaona1 HE Yingchun2,3,4 XU Zhaojun5,6 SONG Lan2,3,4
1.School of Postgraduate, Hu′nan University of Chinese Medicine, Hu′nan Province, Changsha 410208, China;
2.School of Medicine, Hu′nan University of Chinese Medicine, Hu′nan Province, Changsha 410208;
3.Hu′nan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hu′nan Province, Changsha 410208, China;
4.Hu′nan Provincial Ophthalmology and Otolaryngology Diseases Prevention and Treatment with Traditional Chinese Medicine and Visual Function Protection Engineering and Technological Research Center, Hu′nan Province, Changsha 410208, China;
5.Department of Cardiothoracic Surgery, the First Affiliated Hospital of Hu′nan University of Chinese Medicine, Hu′nan Province, Changsha 410000, China;
6.the Domestic First-class Discipline Construction Project of Chinese Medicine of Hu′nan University of Chinese Medicine, Hu′nan Province, Changsha 410000, China
Abstract：Objective To investigate the effects of oleanolic acid on proliferation and apoptosis of lung adenocarcinoma A549 cells, and to explore its mechanism. Methods A549 cells were divided into control group (DMSO), different concentrations of oleanolic acid group (0.625, 1.25, 2.5, 5, 10 μmol/L) and positive control group (Cisplatin, 0.004 g/L) according to different culture methods. MTT and real-time cellular analysis technology (RTCA) were used to detect cell proliferation. Hoechst 33342 staining, mitochondrial membrane potential test, Annexin V-FITC/PI double fluorescent staining were used to detect cell apoptosis. Western blot was used to detect protein expression. Results MTT assay showed that the proliferation rate of A549 cells treated with oleanolic acid at different concentrations for 24, 48 and 72 hours was lower than that of the control group (P < 0.01). The results of RTCA showed that oleanolic acid could inhibit the proliferation of A549 cells. The results of Hoechst 33342 staining showed that compared with the control group, the fluorescence intensity of each group increased significantly (P < 0.05 or P < 0.01). The results of JC-1 staining showed that compared with control group, the red fluorescence intensity decreased significantly and the green fluorescence intensity increased significantly (P < 0.05 or P < 0.01). Annexin V-FITC/PI double fluorescent staining results showed that compared with the control group, the apoptosis of the treated groups increased significantly (P < 0.05 or P < 0.01). Oleanolic acid can down regulate the expression of anti apoptotic protein XIAP, survivin, Bcl-2, up regulate the expression of apoptotic protein Bax, cleaved casepase 3, cleaved caspase 8. Compared with control group, the difference was statistically significant (P < 0.05 or P < 0.01). Conclusion Oleanolic acid can inhibit the proliferation and induce apoptosis of lung adenocarcinoma cells, and its induction of apoptosis may be through the death receptor pathway or the mitochondrial pathway.
李开瑞1 刘洁1 李小娜1 何迎春2,3,4 徐朝军5,6 宋岚2,3,4. 齐墩果酸对肺腺癌A549细胞增殖及凋亡的影响及机制[J]. 中国医药导报, 2019, 16(31): 4-9.
LI Kairui1 LIU Jie1 LI Xiaona1 HE Yingchun2,3,4 XU Zhaojun5,6 SONG Lan2,3,4. Effect and mechanism of oleanolic acid on proliferation and apoptosis of lung adenocarcinoma A549 cells. 中国医药导报, 2019, 16(31): 4-9.
[1] Freddie B，Jacques F. Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin，2018，68（6）：394-424.
[2] Yang CH，Hirsh V. Symptom control and quality of life in LUX-lung 3: a phase Ⅲ study of Afatinib or Cisplatin/Pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations [J]. J Clin Oncol，2013，31（27）：3342-3350.
[3] 李怀东，刘淑磊.我国非小细胞肺癌分子靶向治疗的现实问题及应对建议[J].实用医药杂志，2018，35（4）：91-93，97.
[4] Shanmugam MK，Dai X. Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer：preclinical and clinical evidence [J]. Cancer Lett，2014，346（2）：206-216.
[5] 张明发，沈雅琴.齐墩果酸和熊果酸保肝药理作用的研究进展[J].抗感染药学，2012，9（1）：13-19.
[6] 张明发，沈雅琴.齐墩果酸的药动学研究进展[J].药物评价研究，2017，40（11）：146-152.
[7] 刘玲，黄紫乐.齐墩果酸经线粒体损伤诱导SMMC-7721细胞凋亡的作用[J].中国临床药理学杂志，2017，33（2）：144-148.
[8] 周亚敏，唐洁.夏枯草极性部位的化学成分及其抗乳腺癌活性研究[J].中国药学杂志，2017，52（5）：40-44.
[9] Wei J，Liu H. Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells [J]. Oncol Rep，2012，28（4）：1339-1345.
[10] 柴煊，张振芳.白花蛇舌草不同活性成分抑制肿瘤细胞CT-26增殖的效果[J].武警后勤学院学报：医学版，2016， 25（5）：350-353.
[11] 张明发，沈雅琴.熊果酸和齐墩果酸对肺功能保护和抗肺癌作用的研究进展[J].抗感染药学，2016，13（5）：961-965.
[12] Yan G，Du Q. Application of real-time cell electronic analysis system in modern pharmaceutical evaluation and analysis [J]. Molecules，2018，23（12）：3280.
[13] Cetin I，Topcul MR. Evaluation of the cytotoxic effect of Ly2109761 on Hela cells using the xCELLigence RTCA system [J]. Oncol Lett，2019，17（1）：683-687.
[14] Feng L，Au-Yeung W. Oleanolic acid from Prunella Vulgaris L. induces SPC-A-1 cell line apoptosis via regulation of Bax，Bad and Bcl-2 expression [J]. Asian Pac J Cancer Prev，2011，12（2）：403-408.
[15] 史莲清，冬梅，赵成平.齐墩果酸预处理对大鼠肝脏缺血再灌注损伤中细胞凋亡的影响[J].检验医学与临床，2014，11（A01）：12-15.
[16] 苗俊秋，王效蕊.齐墩果酸诱导人肝癌HepG2细胞凋亡及其作用机制研究[J].现代药物与临床，2016，31（7）：934-938.
[17] Yoo JK，Ji ML. The novel microRNA smR-164 regulates cell proliferation and apoptosis in human lung cancer by targeting XIAP [J]. Lung Cancer，2018，132（1）：99-106.
[18] Yu X，Zhang Y. miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer [J]. Cell Death Dis，2018，9（2）：193.
[19] 牛媛瑕，张艳.阿魏酸诱导胃癌SGC-7901细胞凋亡及对COX-2、Survivin、XIAP和p53的影响[J].西部中医药，2019，32（1）：19-23.
[20] 孙玉洁.白藜芦醇对大鼠脑组织缺血再灌注过程中细胞凋亡及自噬的调剂作用[J].海南医学院学报，2018， 24（1）：5-7.
[21] 吴勃岩，王雪.齐墩果酸对S180荷瘤小鼠细胞色素C和Caspase-3表达的影响[J].中医药信息，2014，31（4）：14-16.
2019, Vol. 16 
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