Experimental Investigation on Reversing Drug Resistance of Non-small Cell Lung Cancer Stem Cells by Aqueous Extract of Taxus Chinensis
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摘要:目的
研究南方红豆杉水提物逆转非小细胞肺癌干细胞耐药作用的机制。
方法选取人非小细胞肺癌H460细胞为实验细胞，以侧群细胞及细胞表面标志物鉴定法筛选出其中的干细胞；CCK8（cell counting kit-8）法检测红豆杉水提物对H460干细胞的毒性，并检测红豆杉水提物逆转H460干细胞对顺铂的耐药性；流式细胞术（flow cytometry,FCM）检测红豆杉水提物逆转H460干细胞耐药的作用机制。
结果红豆杉水提物对H460干细胞有细胞毒性，测得H460干细胞的IC50为1 449.5 μg/ml；用红豆杉水提物预处理后的H460干细胞进行实验发现，顺铂的抗肿瘤效应明显增强，其作用机制为抑制细胞膜上的P-gp蛋白来降低有效药物排出量。
结论南方红豆杉水提物能够较强的逆转非小细胞肺癌干细胞的耐药性。
Abstract:ObjectiveTo investigate the mechanism of aqueous extract of Taxus chinensis(AETC) reversing the drug resistance of non-small cell lung cancer stem cells.
MethodsThe human non-small cell lung cancer cells H460 were chosen to the experiment,and the stem cells were screened from them. The toxicity of AETC was detected with CCK8 method,and the method was also used to check AETC reversing the cisplatin resistance of H460 stem cells. FCM was used to detect the mechanism of AETC reversing the drug resistance of H460 stem cells.
ResultsAETC was toxiferous to H460 stem cells. The IC50 of H460 stem cells was 1449.5 μg/ml. The experiment found the anti-tumor effect of cisplatin was enhanced after H460 stem cells were treated with AETC. The mechanism was related to lower drug elimination through suppressing the P-gp protein on the membrane.
ConclusionAETC could strongly reverse the drug resistance of non-small cell lung cancer stem cells.
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图 1 不同倍数光学显微镜下观察H460干细胞形态
Figure 1 Optical microscopic observation of H460 cells under different multiples
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图 3 红豆杉水提物对H460干细胞耐药性的逆转 (x±s)
Figure 3 Drug resistance reversion of AETC to H460 stem cells (x±s)
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[1] Sui YP, Jian XP, Ma LI, et al. Prognostic value of cancer stem cell marker CD133 expression in esophageal carcinoma: A metaanalysis[ J]. Mol Clin Oncol, 2016, 4(1): 77-82. [1] Sui YP,Jian XP,Ma LI,et al. Prognostic value of cancer stem cell marker CD133 expression in esophageal carcinoma: A meta-analysis[J]. Mol Clin Oncol,2016,4(1): 77-82. http://cn.bing.com/academic/profile?id=2157751472&encoded=0&v=paper_preview&mkt=zh-cn
[2] Leon G, Macdonagh L, Finn SP, et al. Cancer stem cells in drug resistant lung cancer: Targeting cell surface markers and signaling pathways[J]. Pharmacol Ther, 2016, 158: 71-90. [2] Leon G,Macdonagh L,Finn SP,et al. Cancer stem cells in drug resistant lung cancer: Targeting cell surface markers and signaling pathways[J]. Pharmacol Ther,2016,158: 71-90. doi: 10.1016/j.pharmthera.2015.12.001
[3] Adorno-Cruz V, Kibria G, Liu X, et al. Cancer stem cells: targeting the roots of cancer, seeds of metastasis, and sources of therapy resistance[J]. Cancer Res, 2015, 75(6): 924-9. [3] Adorno-Cruz V,Kibria G,Liu X,et al. Cancer stem cells: targeting the roots of cancer,seeds of metastasis,and sources of therapy resistance[J]. Cancer Res,2015,75(6): 924-9. doi: 10.1158/0008-5472.CAN-14-3225
[4] 龚伟, 梅兴国, 鲁翠涛, 等. 红豆杉细胞提取物对肿瘤细胞 SMMC-7721和HEp22的作用研究[J]. 中国药理学通报, 2003, 19(7): 801-3. [Gong W, Mei XG, Lu CT, et al. The extractiong of the Taxus chinensis cells on tumor cell SMMC-7721 and HEp22 action research[J]. Zhongguo Yao Li Xue Tong Bao, 2003, 19(7): 801-3.] [4] 龚伟,梅兴国,鲁翠涛,等. 红豆杉细胞提取物对肿瘤细胞SMMC-7721和HEp22的作用研究[J]. 中国药理学通报,2003,19(7): 801-3. http://www.cnki.com.cn/Article/CJFDTOTAL-YAOL200307019.htm Gong W,Mei XG,Lu CT,et al. The extractiong of the Taxus chinensis cells on tumor cell SMMC-7721 and HEp22 action research[J]. Zhongguo Yao Li Xue Tong Bao,2003,19(7): 801-3.ong W,Mei XG,Lu CT,et al. The extractiong of the Taxus chinensis cells on tumor cell SMMC-7721 and HEp22 action research[J]. Zhongguo Yao Li Xue Tong Bao,2003,19(7): 801-3. http://www.cnki.com.cn/Article/CJFDTOTAL-YAOL200307019.htm
[5] 舒琦瑾,李萍,王彬彬. 南方红豆杉水提物诱导人肺癌A549细胞凋亡及其分子机制的实验研究[J]. 中国中西医结合杂志,2011,31(9): 1243-7. http://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201109032.htm Shu QJ,Li P,Wang BB. Study on Inhibitory action of proliferation of human lung carcinoma A549 cell with aqueous extract of Taxus chinensis[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi,2011,31(9): 1243-7.hu QJ,Li P,Wang BB. Study on Inhibitory action of proliferation of human lung carcinoma A549 cell with aqueous extract of Taxus chinensis[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi,2011,31(9): 1243-7. http://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201109032.htm
[5] 舒琦瑾, 李萍, 王彬彬. 南方红豆杉水提物诱导人肺癌A549细 胞凋亡及其分子机制的实验研究[J]. 中国中西医结合杂志, 2011, 31(9): 1243-7. [Shu QJ, Li P, Wang BB. Study on Inhibitory action of proliferation of human lung carcinoma A549 cell with aqueous extract of Taxus chinensis[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2011, 31(9): 1243-7.] [6] Gu HM, Wang F, Alabi A, et al. Identification of an Amino Acid Residue Critical for Plasma Membrane Localization of ATPBinding Cassette Transporter G1-Brief Report[J]. Arterioscler Thromb Vasc Biol, 2016, 36(2): 253-5. [6] Gu HM,Wang F,Alabi A,et al. Identification of an Amino Acid Residue Critical for Plasma Membrane Localization of ATP-Binding Cassette Transporter G1-Brief Report[J]. Arterioscler Thromb Vasc Biol,2016,36(2): 253-5. doi: 10.1161/ATVBAHA.115.306592
[7] Breitenstein B, Scheuer S, Brückl TM, et al. Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: Results from a randomized clinical study[J]. J Psychiatr Res, 2015, 73: 86-95. [7] Breitenstein B,Scheuer S,Brückl TM,et al. Association of ABCB1 gene variants,plasma antidepressant concentration,and treatment response: Results from a randomized clinical study[J]. J Psychiatr Res,2015,73: 86-95. http://cn.bing.com/academic/profile?id=2177572283&encoded=0&v=paper_preview&mkt=zh-cn
[8] Pang S,Ran Z,Liu Z,et al. Enantioselective induction of a glutathione-S-transferase,a glutathione transporter and an ABC transporter in maize by Metolachlor and its (S)-isomer[J]. PLoS One,2012,7(10): e48085. doi: 10.1371/journal.pone.0048085
[8] Pang S, Ran Z, Liu Z, et al. Enantioselective induction of a glutathione-S-transferase, a glutathione transporter and an ABC transporter in maize by Metolachlor and its (S)-isomer[J]. PLoS One, 2012, 7(10): e48085. [9] Leslie EM. Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs)[J]. J Inorg Biochem, 2012, 108: 141-9. [9] Leslie EM. Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs)[J]. J Inorg Biochem,2012,108: 141-9. doi: 10.1016/j.jinorgbio.2011.11.009
[10] Doss CG,Debottam S,Debajyoti C. Glutathione-responsive nano-transporter-mediated siRNA delivery: silencing the mRNA expression of Ras[J]. Protoplasma,2013,250(3): 787-92. doi: 10.1007/s00709-012-0451-1
[10] Doss CG, Debottam S, Debajyoti C. Glutathione-responsive nano-transporter-mediated siRNA delivery: silencing the mRNA expression of Ras[J]. Protoplasma, 2013, 250(3): 787-92. [11] Sinha C, Ren A, Arora K, et al. Multi-drug resistance protein 4 (MRP4)-mediated regulation of fibroblast cell migration reflects a dichotomous role of intracellular cyclic nucleotides[J]. J Biol Chem, 2013, 288(6): 3786-94. [11] Sinha C,Ren A,Arora K,et al. Multi-drug resistance protein 4 (MRP4)-mediated regulation of fibroblast cell migration reflects a dichotomous role of intracellular cyclic nucleotides[J]. J Biol Chem,2013,288(6): 3786-94. doi: 10.1074/jbc.M112.435925
[12] 徐关兴,孔繁智. 红豆杉—人类健康之树[M]. 北京: 中国时代经济出版社,2009: 59-60. Xu GX,Kong FZ. Taxus chinensis -the tree of human health[M]. Beijing: China Morden Economics Publishing House,2009: 59-60.u GX,Kong FZ. Taxus chinensis -the tree of human health[M]. Beijing: China Morden Economics Publishing House,2009: 59-60.
[12] 徐关兴, 孔繁智. 红豆杉—人类健康之树[M]. 北京: 中国时代 经济出版社, 2009: 59-60. [Xu GX, Kong FZ. Taxus chinensis - the tree of human health[M]. Beijing: China Morden Economics Publishing House, 2009: 59-60.]
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