Inhibition of tanshinone ⅡA on lung cancer cell proliferation
WANG Jiangfeng1, YANG Shiyu2, LI Jianqiang1, CHEN Sheng1
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
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.
[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.
