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| Inhibition of tanshinone ⅡA on lung cancer cell proliferation |
| WANG Jiangfeng1, YANG Shiyu2, LI Jianqiang1, CHEN Sheng1
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1. Department of Thoracic Surgery, Cancer Hospital Affiliated to University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China;
2. Hangzhou Medical College, Hangzhou, Zhejiang 310059, China |
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Abstract Objective To investigate the inhibition of tanshinoneⅡA (TanⅡA) on the proliferation of lung cancer cells. Methods Human lung cancer cell lines A549, SK-MES-1, H446 and H460 were cultured in vitro and treated with TanⅡA at concentrations of 0.3, 0.6, 1.3, 2.5, 5.0, 10.0 mg/mL, while untreated cells served as controls. Cell proliferation was measured by using CCK-8 assay, and apoptosis was measured using flow cytometry, while the expression of apoptosis-related proteins was determined using Western blotting. The apoptotic rate of lung cancer cells was compared between Tan ⅡA-treated cells and untreated cells. Results Tan ⅡA inhibited lung cancer cell proliferation in a time-dependent and concentration-dependent manner, and the survival rates of A549, SK-MS-1, H446 and H460 cells reduced with the concentration of TanⅡA (t=4.503, 2.114, 2.103 and 3.567; all P<0.05) and the duration of TanⅡA treatment (t=5.189, 3.079, 3.023 and 3.845; all P<0.05). The 48 h half maximal inhibitory concentrations (IC50 values) of TanⅡA were (1.18±0.12), (0.78±0.08), (1.55±0.16) and (1.27±0.14) mg/mL against A549, SK-MES-1, H446 and H460 cells, respectively. Following 48 h treatment with Tan ⅡA at a concentration of 2.5 mg/mL, the apoptotic rates of A549, SK-MS-1, H446 and H460 cells were (34.97±3.78)%, (37.62±2.48)%, (18.27±2.98)% and (19.17±2.30)%, which were significantly significantly higher than those of untreated cells [(4.86±0.36) %, (3.21±0.48) %, (3.25±0.26)% and (2.66±0.19)%, all P<0.05]. Reduced Akt1 protein expression, elevated Bax/Bcl-2 expression ratio, and elevated caspase-9 and caspase-3 protein expression were detected in lung cancer cells treated with 2.5 mg/mL TanⅡA for 48 h relative to untreated cells. Conclusion TanⅡA may inhibit lung cancer cell proliferation in a time- and concentration-dependent manner via the Bax/Bcl-2/caspase-9/caspase-3 pathway.
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Received: 30 April 2022
Revised: 21 July 2022
Published: 08 September 2022
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[1] 裘凤黔,杜娟,纪云芳,等.2012—2016年黄浦区恶性肿瘤发病和死亡分析[J].预防医学,2021,33(7):697-700.
QIU F Q,DU J,JI Y F,et al.Morbidity and mortality of cancer in Huangpu District from 2012 to 2016[J].Prev Med,2021,33(7):697-700.
[2] TORRE L A,BRAY F,SIEGEL R L,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3] 方益荣,马岩,许树红,等.肺癌危险因素的病例对照研究[J].预防医学,2019,31(7):649-652.
FANG Y R,MA Y,XU S H,et al.A case control study of risk factors for lung cancer[J].Prev Med,2019,31(7):649-652.
[4] HOY H,LYNCH T,BECK M.Surgical treatment of lung cancer[J].Crit Care Nurs Clin North Am,2019,31(3):303-313.
[5] EL-HUSSEIN A,MANOTO S L,OMBINDA-LEMBOUMBA S,et al.A review of chemotherapy and photodynamic therapy for lung cancer treatment[J].Anticancer Agents Med Chem,2020,20(2):149-161.
[6] VINOD S K,HAU E.Radiotherapy treatment for lung cancer:current status and future directions[J].Respirology,2020,25(2):61-71.
[7] 杨渊,陈楠,马千里,等.阿帕替尼联合大剂量丹参酮ⅡA对肺腺癌A549细胞株凋亡及Bim异构体影响[J].现代肿瘤医学,2019,27(8):1319-1323.
YANG Y,CHEN N,MA Q L,et al.Effect of combination of apatinib and high-dose tanshinone ⅡA on apoptosis and Bim isomers of lung adenocarcinoma A549 cell line[J].J Mod Oncol,2019,27(8):1319-1323.
[8] 李娜. 丹参酮ⅡA对人肺癌细胞H2009凋亡的影响[J].四川医学,2022,43(3):222-226.
LI N.Effect of tanshinone ⅡA on apoptosis of human lung cancer cells H2009[J].Sichuan Med J,2022,43(3):222-226.
[9] 王介营,李芹,徐蒙,等.EGF及其受体在丹参酮ⅡA抑制甲状腺癌细胞增殖中的作用及其机制[J].国际医药卫生导报,2020,26(5):669-673.
WANG J Y,LI Q,XU M,et al.Effect and mechanisms of tanshinone ⅡA on the expression of EGF and EGFR in thyroid cancer cells[J].Int Med Health Guid News,2020,26(5):669-673.
[10] ZHANG X,ZHOU Y,GU Y E.Tanshinone ⅡA induces apoptosis of ovarian cancer cells in vitro and in vivo through attenuation of PI3K/AKT/JNK signaling pathways[J].Oncol Lett,2018,17(2):1896-1902.
[11] WON S H,LEE H J,JEONG S J,et al.Tanshinone ⅡA induces mitochondria dependent apoptosis in prostate cancer cells in association with an inhibition of phosphoinositide 3-kinase/AKT pathway[J].Biol Pharm Bull,2010,33(11):1828-1834.
[12] LI Y,WANG Y,YU X,et al.Radix Tetrastigma inhibits the non-small cell lung cancer via Bax/Bcl-2/Caspase-9/Caspase-3 pathway[J].Nutr Cancer,2021,74(1):320-332.
[13] SU C C,LIN Y H.Tanshinone ⅡA inhibits human breast cancer cells through increased Bax to Bcl-xL ratios[J].Int J Mol Med,2008,22(3):357-361.
[14] SU C.Growth inhibition and apoptosis induction by tanshinone I in human colon cancer Colo 205 cells[J].Int J Mol Med,2008,22(5):613-618.
[15] ASHOKKUMAR T,PRABHU D,GEETHA R,et al.Apoptosis in liver cancer(HepG2)cells induced by functionalized gold nanoparticles[J].Colloids Surf B Biointerfaces,2014,123:549-556.
[16] BRENTNALL M,RODRIGUEZ-MENOCAL L,DE GUEVARA R L,et al.Caspase-9,caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis[J/OL].BMC Cell Biol,2013,14[2022-07-21].http://www.biomedcentral.com/1471-2121/14/32.
[17] LI L Y,LUO X,WANG X.Endonuclease G is an apoptotic DNase when released from mitochondria[J].Nature,2001,412(6842):95-99.
[18] ZHANG C C,LI C G,WANG Y F,et al.Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation[J].Apoptosis,2019,24(3/4):312-325.
[19] WANG W T,ZHU M Y,XU Z X,et al.Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity[J/OL].Biol Res,2019,52(1)[2022-07-21].https://doi.org/10.1186/s40659-019-0242-7.
[20] 徐兴军,李珊珊,刘畅,等.川楝素诱导人胃癌MGC-803细胞凋亡及其机制[J].中国应用生理学杂志,2021,37(3):262-265.
XU X J,LI S S,LIU C,et al.Toosendanin induces apoptosis of human gastric cancer MGC-803 cells and its mechanism[J].Chin J Appl Physiol,2021,37(3):262-265. |
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