1.桂林医学院 药学院,广西 桂林 541004
2.广西肝脏损伤与修复分子医学重点实验室,广西 桂林 541004
王 玲,女,硕士生,现从事药物作用于肿瘤相关机制的研究。 E⁃mail: 2305570599@qq.com
E⁃mail:35112908@qq.com
纸质出版日期:2019-08-24,
收稿日期:2018-01-22,
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王玲,李居伟,杨扬.石蒜碱对Lewis肺癌小鼠的抑瘤作用及机制[J].武汉大学学报(理学版),2019,65(04):363-368.
WANG Ling,LI Juwei,YANG Yang.Anti⁃Tumor Effect and Mechanism of Lycorine on Lewis Lung Cancer Mice[J].J Wuhan Univ (Nat Sci Ed),2019,65(04):363-368.
王玲,李居伟,杨扬.石蒜碱对Lewis肺癌小鼠的抑瘤作用及机制[J].武汉大学学报(理学版),2019,65(04):363-368. DOI: 10.14188/j.1671-8836.2019.04.007.
WANG Ling,LI Juwei,YANG Yang.Anti⁃Tumor Effect and Mechanism of Lycorine on Lewis Lung Cancer Mice[J].J Wuhan Univ (Nat Sci Ed),2019,65(04):363-368. DOI: 10.14188/j.1671-8836.2019.04.007.
建立Lewis肺癌小鼠移植瘤模型,以10、14、20、28、40 mg/kg 5个剂量组给药,探讨石蒜碱的抑瘤作用及机制,采用HE染色法观察肿瘤细胞的形态学变化,通过免疫组化实验观察石蒜碱对瘤体细胞凋亡相关因子Fas⁃L、Caspase⁃9、Bax、Bcl⁃2表达的影响。石蒜碱对Lewis肺癌小鼠的抑瘤率随着剂量的增加而增大,高剂量组(40 mg/kg)石蒜碱对Lewis肺癌小鼠的抑瘤作用最明显,抑瘤率达56.8%(,p<,0.01);HE染色结果显示高剂量组(40 mg/kg)小鼠瘤组织细胞间隙增大,细胞数目明显减少;免疫组化实验结果表明石蒜碱可通过上调促凋亡蛋白Fas⁃L、Caspase⁃9、Bax,下调抑凋亡蛋白Bcl⁃2,促进肺癌Lewis细胞凋亡。
A xenograft mouse model of Lewis lung cancer was established to investigate the anti⁃tumor effect and mechanism, which was administered in 5 dose groups of 10, 14, 20, 28, 40 mg/kg of Lycorine. HE staining was used to detect the morphological changes of mouse tumor cells. The apoptosis⁃related proteins (Fas⁃L, Caspase⁃9, Bax, and Bcl⁃2) were detected by immunohistochemistry experiments. It is found that the inhibition rate increased with the increase of dosage of Lycorine on lung cancer mice. And the high dose of Lycorine (40 mg/kg) had the most obvious anti⁃tumor activity in Lewis lung cancer mice, with the inhibition rate of 56.8% (,p,<,0.01). HE staining results reveal that intercellular space is magnified and the number of cells is significantly decreased in the high⁃dose group (40 mg/kg). It shows that Lycorine can promote Lewis lung cancer cell apoptosis in solid tumors by up⁃regulating the pro⁃apoptotic proteins of Fas⁃L, Caspase⁃9, Bax and down⁃regulating the anti⁃apoptotic protein of Bcl⁃2 with immunohistochemistry.
石蒜碱Lewis肺癌细胞抑瘤作用细胞凋亡
LycorineLewis lung cancer cellanti⁃tumor effectapoptosis
WINGO P A, RIES L A, GIOVINO G A, et al. Annual report to the nation on the status of cancer, 1973⁃1996, with a special section on lung cancer and tobacco smoking [J]. Journal of the National Cancer Institute, 1999, 91(8): 675⁃690. DOI:10.1093/jnci/91.8.675http://dx.doi.org/10.1093/jnci/91.8.675.
林贵山, 程惠华, 傅志超, 等. 晚期非小细胞肺癌同步放化疗的疗效分析[J]. 中华放射肿瘤学杂志, 2006, 15(6): 462⁃466. DOI: 10.3760/j.issn.1004-4221.2006.06.008http://dx.doi.org/10.3760/j.issn.1004⁃4221.2006.06.008.
LIN G S, CHENG H H, FU Z C, et al. Compairson of coneurrnt chemo⁃aridohterapy and sequential chemo⁃aridohterapy for locally advanced non⁃small lung cancer [J]. Chinese Journal of Radiation Oncology, 2006, 15(6): 462⁃466. DOI: 10.3760/j.issn.1004-4221.2006.06.008(Chhttp://dx.doi.org/10.3760/j.issn.1004⁃4221.2006.06.008(Ch).
胡坚, 包飞潮. 早期非小细胞肺癌外科治疗新进展[J]. 中国肺癌杂志, 2016, 19(6): 399⁃402. DOI:3779/j.issn.1009-3419.2016.06.20http://dx.doi.org/3779/j.issn.1009⁃3419.2016.06.20.
HU J, BAO F C. Advances in surgical treatment of early stage non⁃small cell lung cancer [J]. Chinese Journal of Lung Cancer, 2016, 19(6): 399⁃402. DOI: 10.3779/j.issn.1009-3419.2016.06.20(Chhttp://dx.doi.org/10.3779/j.issn.1009⁃3419.2016.06.20(Ch).
孙伟. 经皮射频消融与手术切除治疗小肝癌的临床效果比照观察[J]. 中国医药指南, 2017(26): 78⁃79. DOI:10.15912/j.cnki.gocm.2017.26.062http://dx.doi.org/10.15912/j.cnki.gocm.2017.26.062.
SUN W. Comparison observation of clinical effects of percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinoma [J]. Guide of China Medicine, 2017(26): 78⁃79. DOI:10.15912/j.cnki.gocm.2017.26.062(Chhttp://dx.doi.org/10.15912/j.cnki.gocm.2017.26.062(Ch).
贾献慧, 周铜水, 郑颖. 石蒜科植物生物碱成分的药理学研究[J]. 中医药学刊, 2001, 19(6): 573⁃574. DOI:10.3969/j.issn.1673-7717.2001.06.022http://dx.doi.org/10.3969/j.issn.1673⁃7717.2001.06.022.
JIA X H, ZHOU T S, ZHENG Y, et al. The pharmacological study of alkaloid ingredient contained in Amaryllidaceae plant [J]. Study Journal of Traditional Chinese Medicine, 2001, 19(6): 573⁃574. DOI: 10.3969/j.issn.1673-7717.2001.06.022(Chhttp://dx.doi.org/10.3969/j.issn.1673⁃7717.2001.06.022(Ch).
季宇彬, 辛国松, 曲中原, 等. 石蒜属植物生物碱类化学成分和药理作用研究进展[J]. 中草药, 2016, 47(1). DOI: 10.7501/j.issn.0253-2670.2016.01.024http://dx.doi.org/10.7501/j.issn.0253⁃2670.2016.01.024.
JI Y B, XIN G S, QU Z Y, et al. Research progress on chemical constituents and pharmacological effects of alkaloids from plants of Lycoris herb[J]. Chinese Traditional and Herbal Drugs, 2016, 47(1). DOI: 10.7501/j.issn.0253-2670.2016.01.024(Chhttp://dx.doi.org/10.7501/j.issn.0253⁃2670.2016.01.024(Ch).
王杨, 于淼. 石蒜碱诱导人白血病K562细胞凋亡的研究[J]. 哈尔滨商业大学学报(自然科学版), 2015, 31(2): 135⁃139. DOI: 10.3969/j.issn.1672-0946.2015.02.003http://dx.doi.org/10.3969/j.issn.1672⁃0946.2015.02.003.
WANG Y, YU M. Study on Lycorine⁃induced apoptosis of human K562 cells [J]. Journal of Harbin University of Commerce (Natural Sciences Edition), 2015, 31(2): 135⁃139. DOI: 10.3969/j.issn.1672-0946.2015.02.003(Chhttp://dx.doi.org/10.3969/j.issn.1672⁃0946.2015.02.003(Ch).
季宇彬,辛国松,魏驰,等.石蒜碱诱导人肝癌HepG2细胞自噬的体外实验研究[J].中药材, 2018, 41(6): 1449⁃1454. DOI: 10.13863/j.issn1001-4454.2018.06.041http://dx.doi.org/10.13863/j.issn1001⁃4454.2018.06.041.
JI Y B, XIN G S, WEI C, et al. Experimental study on the autophagy of HepG2 cells in human liver cancer induced by Lycorine in vitro [J]. Journal of Chinese Medicinal Materials, 2018, 41(6): 1449⁃1454. DOI: 10.13863/j.issn1001-4454.2018.06.041(Chhttp://dx.doi.org/10.13863/j.issn1001⁃4454.2018.06.041(Ch).
YU H Y, QIU Y L, PANG X, et al. Lycorine promotes autophagy and apoptosis via TCRP1/Akt/mTOR axis inactivation in human hepatocellular carcinoma [J]. Molecular Cancer Therapeutics, 2017, 16(12): 2711⁃2723. DOI: 10.1158/1535-7163.MCT-17-0498http://dx.doi.org/10.1158/1535⁃7163.MCT⁃17⁃0498.
陈肖, 龙潇鸿, 廖渝, 等. 石蒜碱通过下调细胞周期蛋白D1表达抑制SGC⁃7901胃癌细胞增殖并促进其凋亡[J]. 细胞与分子免疫学杂志, 2018, 34(4): 354⁃358. DOI: 10.13423/j.cnki.cjcmi.008586http://dx.doi.org/10.13423/j.cnki.cjcmi.008586.
CHEN X, LONG X H, LIAO Y, et al. Lycorine inhibits the proliferation and promotes apoptosis of SGC⁃7901 gastric cancer cells by downregulating expression of cyclin D1 [J]. Chinese Journal of Cellular and Molecular Immunology, 2018, 34(4): 354⁃358. DOI: 10.13423/j.cnki.cjcmi.008586(Chhttp://dx.doi.org/10.13423/j.cnki.cjcmi.008586(Ch).
刘希宇, 贺小英, 王凤梅, 等. 石蒜碱对人胃癌细胞体外增殖的影响[J]. 信阳师范学院学报(自然科学版), 2015, 28(2): 173⁃176. DOI: 10.3969/j.issn.1003-0972.2015.02.005http://dx.doi.org/10.3969/j.issn.1003⁃0972.2015.02.005.
LIU X Y, HE X Y, WANG F M, et al. The influence of Lycorisradiata Alkali on the proliferation of human gastric cancer cells cultured in vitro [J]. Journal of Xinyang Normal University (Natural Science Edition), 2015, 28(2): 173⁃176. DOI: 10.3969/j.issn.1003-0972.2015.02.005(Chhttp://dx.doi.org/10.3969/j.issn.1003⁃0972.2015.02.005(Ch).
姚佳, 李世正, 杜煜, 等. 石蒜碱诱导结肠癌HT⁃29细胞凋亡机制研究[J]. 现代预防医学, 2018, 45(13): 2408⁃2412.
YAO J, LI S Z, DU Y, et al. Mechanism of apoptosis induced by Lycorine in colon cancer HT⁃29 cells [J]. Modern Preventive Medicine, 2018, 45(13): 2408⁃2412(Ch).
WANG C S, WANG Q R, LI X Z, et al. Lycorine induces apoptosis of bladder cancer T24 cells by inhibiting phospho⁃Akt and activating the intrinsic apoptotic cascade [J]. Biochemical and Biophysical Research Communications, 2017, 483(1):197⁃202. DOI:10.1016/j.bbrc.2016.12.168http://dx.doi.org/10.1016/j.bbrc.2016.12.168.
LAMORAL⁃THEYS D, DECAESTECKER C, MA⁃THIEU V, et al. Lycorine and its derivatives for anticancer drug design [J]. Mini⁃Reviews in Medicinal Chemistry, 2010, 10(1): 41⁃50. DOI: 10.2174/138955710791 112604http://dx.doi.org/10.2174/138955710791112604.
果婷婷, 王辉强, 李玉环, 等. 石蒜碱及其衍生物的药理作用研究进展[J]. 中国医药生物技术, 2018, 13(5): 463⁃466. DOI: 10.3969/j.issn.1673-713X.2018.05.014http://dx.doi.org/10.3969/j.issn.1673⁃713X.2018.05.014.
GUO T T, WANG H Q, LI Y H, et al. Research progress on pharmacological effects of Lycorine and its derivatives [J]. Chinese Medicinal Biotechnology, 2018, 13(5): 463⁃466.DOI: 10.3969/j.issn.1673-713X.2018.05.014(Chhttp://dx.doi.org/10.3969/j.issn.1673⁃713X.2018.05.014(Ch).
张炜, 崔恩海. 石蒜碱诱导肺癌A549细胞凋亡作用研究[J]. 中国中药杂志, 2015, 40(16): 3278⁃3282. DOI: 10.4268/cjcmm20151630http://dx.doi.org/10.4268/cjcmm20151630.
ZHANG W, CUI E H. Study on effect of Lycorine in inducing apoptosis of pulmonary carcinoma cell A549 [J]. China Journal of Chinese Materia, 2015, 40(16): 3278⁃3282. DOI: 10.4268/cjcmm20151630(Chhttp://dx.doi.org/10.4268/cjcmm20151630(Ch).
ZENG H, FU R, YAN L X, et al. Lycorine induces apoptosis of A549 cells via AMPK⁃Mammalian target of rapamycin (mTOR)⁃S6K signaling pathway [J]. Medical Science Monitor, 2017, 23: 2035⁃2041. DOI:10.12659/MSM.900742http://dx.doi.org/10.12659/MSM.900742.
李居伟, 杨扬. 石蒜碱诱导肺癌NCI⁃H460细胞凋亡作用及其机制[J]. 肿瘤防治研究, 2018, 45(1): 5⁃8. DOI: 10.3971/j.issn.1000-8578.2018.17.0388http://dx.doi.org/10.3971/j.issn.1000⁃8578.2018.17.0388.
LI J W, YANG Y. Apoptosis of NCI⁃H460 cells induced by Lycorine in lung cancer [J]. Cancer Research on Prevention and Treatment, 2018, 45(1): 5⁃8. DOI: 10.3971/j.issn.1000-8578.2018.17.0388(Chhttp://dx.doi.org/10.3971/j.issn.1000⁃8578.2018.17.0388(Ch).
STONEMEN V E, BENNETT M R. Role of Fas/Fas⁃L in vascular cell apoptosis [J]. Journal of Cardiovascular Pharmacology, 2009, 53(2): 100⁃108. DOI: 10.1097/FJC.0b013e318198fe60http://dx.doi.org/10.1097/FJC.0b013e318198fe60.
BABU P P, SUZUKI G, ONO Y, et al. Attenuation of ischemia and /or reperfusion injury during myocardial infarction using mild hypothermia in rats: An immunohistochemical study of Bcl⁃2, Bax, Bak and TUNEL [J]. Pathology International, 2004, 54(12): 896⁃903. DOI: 10.1111/j.1440-1827.2004.01767.xhttp://dx.doi.org/10.1111/j.1440⁃1827.2004.01767.x.
胡家才, 李清泉. 川芎嗪对肺癌A549细胞增殖与凋亡的影响及其机制[J]. 武汉大学学报(医学版), 2010, 31(1): 19⁃21. DOI:10.14188/j.1671-8852.2010.01.025http://dx.doi.org/10.14188/j.1671⁃8852.2010.01.025.
HU J C, LI Q Q. Effect of tetramethypyrazine on the proliferation and apoptosis of lung cancer cell line of A549 and its mechanism [J]. Medical Journal of Wuhan University, 2010, 31(1): 19⁃21. DOI:10.14188/j.1671-8852.2010.01.025(Chhttp://dx.doi.org/10.14188/j.1671⁃8852.2010.01.025(Ch).
SCHON E A, MANFREDI G. Neuronal degeneration and mitochondrial dysfunction [J]. The Journal of Clinical Investagion, 2003, 111(3): 303⁃312. DOI: 10.1172/JCI17741http://dx.doi.org/10.1172/JCI17741. □
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