Effect of 17-AAG Combining with Paclitaxel on Proliferation and Apoptosis of Human Anaplastic Thyroid Cancer FRO Cell Line_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIUYang ¹ ,  WUGao-song ² , WANGWen-bin ¹ , MIAOWen-qing ¹ , HUANGMing ¹ , CHENDa-ping ¹

1. Department of Breast and Thyroid Surgery, Xianning Hospital of Tongji, Xianning Central Hospital, Xianning 437000, Hubei Province, China;
2. Department of Breast and Thyroid Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China;

Corresponding author：

WUGao-song, Email: wugaosongtj@163.com

Keywords：

propylene amino-17-demethoxy geldanamycin; Paclitaxel; Heat shock protein 90; Synergism

DOI：

10.7507/1007-9424.20160080

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the inhibitory effect of heat shock protein 90 (HSP90) inhibitors of 17-propylene amino-17-demethoxy geldanamycin (17-AAG) combining with paclitaxel on human anaplastic thyroid cancer FRO cell line. Method ①The proliferation inhibition rates of FRO cells were detected by mmethyl thiazolyl tetrazolium (MTT) assay in different concentration groups (17-AAG: 0.312 5, 0.625 0, 1.2500, 2.5000, and 5.0000 μmol/L; paclitaxel: 0.001 0, 0.0100, 0.1000, and 1.0000 μmol/L; combination group, 17-AAG: 0.625 0 μmol/L, paclitaxel: 0.001 0, 0.0100, 0.1000, and 1.0000 μmol/L) and at different time points (24, 48, and 72 hours). ②The change of cell cycle and apoptosis rates of FRO cells were detected in 17-AAG group (0.625 0 μmol/L), paclitaxel group (0.1000 μmol/L), and combination group (17-AAG: 0.625 0 μmol/L, paclitaxel: 0.1000 μmol/L) by flow cytometry at 24 hours after treatment. ③activity of Caspase-3 and Caspase-9 in FRO cells of 17-AAG group (0.625 0 μmol/L), paclitaxel group (0.1000 μmol/L), and combination group (17-AAG: 0.625 0 μmol/L, paclitaxel: 0.1000 μmol/L) was detected by Caspase-3 detection reagent box and Caspase-9 detection reagent box respectively. FRO cells of normal control group were treated without any drug, but culture solution. Results ①The proliferation inhibition rates of FRO cells increased with the increase of concentra-tion (17-AAG, paclitaxel, combination of 17-AAG and paclitaxel), there was significant difference between any 2 groups (normal control group included), P<0.05. In addition, the proliferation inhibition rates of FRO cells in any concentration group (normal control group excluded) increased over time (24, 48, and 72 hours), there was significant difference between any 2 time points (P<0.05). The proliferation inhibition rates of FRO cells in combination group were all higher than those of 17-AAG group and paclitaxel group in condition of same time point and same concentration (P<0.05). The q value of combination group was higher than 1.15 at 3 time points in all concentration, that meant 17-AAG could increase the efficiency of paclitaxel. ②The apoptosis rate of FRO cells in normal control group was lower than those of 17-AAG group, paclitaxel group, and combination group (P<0.05), and apoptosis rate of FRO cells in combination group was higher than those of 17-AAG group and paclitaxel group (P<0.05). ③Activity of Caspase-3 and Caspase-9 of FRO cells in normal control group were lower than those of 17-AAG group, paclitaxel group, and combination group (P<0.05), and activity of Caspase-3 and Caspase-9 of FRO cells in combination group were higher than those of 17-AAG group and paclitaxel group (P<0.05). Conclusions 17-AAG and paclitaxel can significantly inhibit the proliferation and induce the apoptosis of FRO cells. The combination of the two kinds of drugs may generate synergy, with dose-dependence effect.

Citation： LIUYang, WUGao-song, WANGWen-bin, MIAOWen-qing, HUANGMing, CHENDa-ping. Effect of 17-AAG Combining with Paclitaxel on Proliferation and Apoptosis of Human Anaplastic Thyroid Cancer FRO Cell Line. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(3): 292-296. doi: 10.7507/1007-9424.20160080 Copy

1.	茅晓东, 陈国芳, 徐书杭, 等. 索拉非尼与二甲双胍对甲状腺未分化癌细胞株的生长抑制作用. 中华内分泌代谢杂志, 2013, 29(7): 608-612.
2.	Sherman SI. Thyroid carcinoma. Lancet, 2003, 361(9356): 501-511.
3.	Jhaveri K, Taldone T, Modi S, et al. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim Biophys Acta, 2012, 1823(3): 742-755.
4.	沈艳丽, 高向东, 顾觉奋. Hsp90抑制剂的研究. 国外医药: 抗生素分册, 2013, 34(4): 145-148.
5.	金正均. 合并用药中的相加. 中国药理学报, 1980, 1(2): 70-76.
6.	靳梦亚, 董玲, 戴俊东, 等. Bradford法测量不同加工工艺鹿茸蛋白含量研究. 中华中医药学刊, 2015, 33(3): 592-594.
7.	O'Neill JP, Shaha AR. Anaplastic thyroid cancer. Oral Oncol, 2013, 49(7): 702-706.
8.	Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA, 2006, 295(18): 2164-2167.
9.	王新征, 刘金彪, 侯永强, 等. 分化型甲状腺癌组织中HSP70与TNF-α的表达及与临床病理的相关性. 中国老年学杂志, 2015, 35(1): 112-113.
10.	Aschebrook-Kilfoy B, Ward MH, Sabra MM, et al. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Throid, 2011, 21(2): 125-134.
11.	陈强, 张其忠, 刘健, 等. 紫杉醇脂质体与传统紫杉醇治疗乳腺癌和非小细胞肺癌的随机对照研究. 中华肿瘤杂志, 2003, 25(2): 190-192.
12.	杨振磊, 张四喜, 黄桂华, 等. 抗肿瘤药紫杉醇载体的研究进展. 中国生化药物杂志, 2015, 35(9): 183-185.
13.	Sunters A, Madureira PA, Pomeranz KM, et al. Paclitaxel-induced nuclear translocation of FOXO3a in breast cancer cells is mediated by c-Jun NH2-terminal kinase and Akt. Cancer Res, 2006, 66(1): 212-220.
14.	Soroka J, Wandinger SK, Mäusbacher N, et al. Conformational switching of the molecular chaperone Hsp90 via regulated phosphor-ylation. Mol Cell, 2012, 45(4): 517-528.
15.	Woyach JA, Shah MH. New therapeutic advances in the manage-ment of progressive thyroid cancer. Endocr Relat Cancer, 2009, 16(3): 715-731.
16.	宋媛媛, 韩晓红, 郑翠玲, 等. ELISA检测肿瘤患者热休克蛋白90α的影响因素分析. 中华检验医学杂志, 2013, 36(12): 1100-1103.
17.	朱奇, 祝宇, 徐云泽, 等. 热休克蛋白抑制剂对嗜铬细胞瘤裸鼠移植瘤的抑制作用. 国际泌尿系统杂志, 2014, 34(5): 641-645.
18.	Wang SX, Ju HQ, Liu KS, et al. SNX-2112, a novel Hsp90 inhibitor, induces G2 /M cell cycle arrest and apoptosis in MCF-7 cells. Biosci Biotechnol Biochem, 2011, 75(8): 1540-1545.
19.	赵学荣, 王建平, 肖丽君, 等. 17-AAG阻滞HCT-15细胞周期并诱导其凋亡. 中国病理生理杂志, 2015, 31(1): 98-103.
20.	Visan I. Inflammasome caspase. Nature Immunol, 2012, 13(4): 358.
21.	Li C, Wu JJ, Hynes M, et al. C-met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology, 2011, 141(6): 2218-2227.
22.	陈爱华, 于皆平. 胰腺癌组织中Survivin和CasPase-3蛋白的表达与患者临床病理特征及生存期的关系. 现代中西医结合杂志, 2015, 24(15): 1625-1627.
23.	潘科, 卢书明, 于劲达, 等. 胃癌及癌前病变细胞凋亡与caspase9, Bax表达的关系. 现代肿瘤医学, 2010, 18(2): 317-319.
24.	殷舞, 莫祥兰, 韦海明, 等. Survivin、Apaf-1和caspase9在胃癌腹膜转移中的表达及意义. 广东医学, 2014, 35(2): 221-223.
25.	金彬, 玄云泽, 李京旭, 等. 术前间质化疗对口腔鳞状细胞癌中Ki-67、Caspase-3蛋白的影响. 重庆医学, 2014, 43(14): 1707-1709.
26.	艾毅钦, 汪勇, 赵川, 等. Caspase-9蛋白表达水平对预测直肠癌术前放化疗敏感性的临床意义. 昆明医科大学学报, 2014, 35(10): 70-75.

1. 茅晓东, 陈国芳, 徐书杭, 等. 索拉非尼与二甲双胍对甲状腺未分化癌细胞株的生长抑制作用. 中华内分泌代谢杂志, 2013, 29(7): 608-612.
2. Sherman SI. Thyroid carcinoma. Lancet, 2003, 361(9356): 501-511.
3. Jhaveri K, Taldone T, Modi S, et al. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim Biophys Acta, 2012, 1823(3): 742-755.
4. 沈艳丽, 高向东, 顾觉奋. Hsp90抑制剂的研究. 国外医药: 抗生素分册, 2013, 34(4): 145-148.
5. 金正均. 合并用药中的相加. 中国药理学报, 1980, 1(2): 70-76.
6. 靳梦亚, 董玲, 戴俊东, 等. Bradford法测量不同加工工艺鹿茸蛋白含量研究. 中华中医药学刊, 2015, 33(3): 592-594.
7. O'Neill JP, Shaha AR. Anaplastic thyroid cancer. Oral Oncol, 2013, 49(7): 702-706.
8. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA, 2006, 295(18): 2164-2167.
9. 王新征, 刘金彪, 侯永强, 等. 分化型甲状腺癌组织中HSP70与TNF-α的表达及与临床病理的相关性. 中国老年学杂志, 2015, 35(1): 112-113.
10. Aschebrook-Kilfoy B, Ward MH, Sabra MM, et al. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Throid, 2011, 21(2): 125-134.
11. 陈强, 张其忠, 刘健, 等. 紫杉醇脂质体与传统紫杉醇治疗乳腺癌和非小细胞肺癌的随机对照研究. 中华肿瘤杂志, 2003, 25(2): 190-192.
12. 杨振磊, 张四喜, 黄桂华, 等. 抗肿瘤药紫杉醇载体的研究进展. 中国生化药物杂志, 2015, 35(9): 183-185.
13. Sunters A, Madureira PA, Pomeranz KM, et al. Paclitaxel-induced nuclear translocation of FOXO3a in breast cancer cells is mediated by c-Jun NH2-terminal kinase and Akt. Cancer Res, 2006, 66(1): 212-220.
14. Soroka J, Wandinger SK, Mäusbacher N, et al. Conformational switching of the molecular chaperone Hsp90 via regulated phosphor-ylation. Mol Cell, 2012, 45(4): 517-528.
15. Woyach JA, Shah MH. New therapeutic advances in the manage-ment of progressive thyroid cancer. Endocr Relat Cancer, 2009, 16(3): 715-731.
16. 宋媛媛, 韩晓红, 郑翠玲, 等. ELISA检测肿瘤患者热休克蛋白90α的影响因素分析. 中华检验医学杂志, 2013, 36(12): 1100-1103.
17. 朱奇, 祝宇, 徐云泽, 等. 热休克蛋白抑制剂对嗜铬细胞瘤裸鼠移植瘤的抑制作用. 国际泌尿系统杂志, 2014, 34(5): 641-645.
18. Wang SX, Ju HQ, Liu KS, et al. SNX-2112, a novel Hsp90 inhibitor, induces G2 /M cell cycle arrest and apoptosis in MCF-7 cells. Biosci Biotechnol Biochem, 2011, 75(8): 1540-1545.
19. 赵学荣, 王建平, 肖丽君, 等. 17-AAG阻滞HCT-15细胞周期并诱导其凋亡. 中国病理生理杂志, 2015, 31(1): 98-103.
20. Visan I. Inflammasome caspase. Nature Immunol, 2012, 13(4): 358.
21. Li C, Wu JJ, Hynes M, et al. C-met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology, 2011, 141(6): 2218-2227.
22. 陈爱华, 于皆平. 胰腺癌组织中Survivin和CasPase-3蛋白的表达与患者临床病理特征及生存期的关系. 现代中西医结合杂志, 2015, 24(15): 1625-1627.
23. 潘科, 卢书明, 于劲达, 等. 胃癌及癌前病变细胞凋亡与caspase9, Bax表达的关系. 现代肿瘤医学, 2010, 18(2): 317-319.
24. 殷舞, 莫祥兰, 韦海明, 等. Survivin、Apaf-1和caspase9在胃癌腹膜转移中的表达及意义. 广东医学, 2014, 35(2): 221-223.
25. 金彬, 玄云泽, 李京旭, 等. 术前间质化疗对口腔鳞状细胞癌中Ki-67、Caspase-3蛋白的影响. 重庆医学, 2014, 43(14): 1707-1709.
26. 艾毅钦, 汪勇, 赵川, 等. Caspase-9蛋白表达水平对预测直肠癌术前放化疗敏感性的临床意义. 昆明医科大学学报, 2014, 35(10): 70-75.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of 17-AAG Combining with Paclitaxel on Proliferation and Apoptosis of Human Anaplastic Thyroid Cancer FRO Cell Line

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