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.	茅曉東, 陳國芳, 徐書杭, 等. 索拉非尼與二甲雙胍對甲狀腺未分化癌細胞株的生長抑制作用. 中華內分泌代謝雜志, 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.	沈艷麗, 高向東, 顧覺奮. Hsp90抑制劑的研究. 國外醫藥: 抗生素分冊, 2013, 34(4): 145-148.
5.	金正均. 合并用藥中的相加. 中國藥理學報, 1980, 1(2): 70-76.
6.	靳夢亞, 董玲, 戴俊東, 等. Bradford法測量不同加工工藝鹿茸蛋白含量研究. 中華中醫藥學刊, 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, 劉金彪, 侯永強, 等. 分化型甲狀腺癌組織中HSP70與TNF-α的表達及與臨床病理的相關性. 中國老年學雜志, 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.	陳強, 張其忠, 劉健, 等. 紫杉醇脂質體與傳統紫杉醇治療乳腺癌和非小細胞肺癌的隨機對照研究. 中華腫瘤雜志, 2003, 25(2): 190-192.
12.	楊振磊, 張四喜, 黃桂華, 等. 抗腫瘤藥紫杉醇載體的研究進展. 中國生化藥物雜志, 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, M?usbacher 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, 韓曉紅, 鄭翠玲, 等. ELISA檢測腫瘤患者熱休克蛋白90α的影響因素分析. 中華檢驗醫學雜志, 2013, 36(12): 1100-1103.
17.	朱奇, 祝宇, 徐云澤, 等. 熱休克蛋白抑制劑對嗜鉻細胞瘤裸鼠移植瘤的抑制作用. 國際泌尿系統雜志, 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.	趙學榮, 王建平, 肖麗君, 等. 17-AAG阻滯HCT-15細胞周期并誘導其凋亡. 中國病理生理雜志, 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.	陳愛華, 于皆平. 胰腺癌組織中Survivin和CasPase-3蛋白的表達與患者臨床病理特征及生存期的關系. 現代中西醫結合雜志, 2015, 24(15): 1625-1627.
23.	潘科, 盧書明, 于勁達, 等. 胃癌及癌前病變細胞凋亡與caspase9, Bax表達的關系. 現代腫瘤醫學, 2010, 18(2): 317-319.
24.	殷舞, 莫祥蘭, 韋海明, 等. Survivin、Apaf-1和caspase9在胃癌腹膜轉移中的表達及意義. 廣東醫學, 2014, 35(2): 221-223.
25.	金彬, 玄云澤, 李京旭, 等. 術前間質化療對口腔鱗狀細胞癌中Ki-67、Caspase-3蛋白的影響. 重慶醫學, 2014, 43(14): 1707-1709.
26.	艾毅欽, 汪勇, 趙川, 等. Caspase-9蛋白表達水平對預測直腸癌術前放化療敏感性的臨床意義. 昆明醫科大學學報, 2014, 35(10): 70-75.

1. 茅曉東, 陳國芳, 徐書杭, 等. 索拉非尼與二甲雙胍對甲狀腺未分化癌細胞株的生長抑制作用. 中華內分泌代謝雜志, 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. 沈艷麗, 高向東, 顧覺奮. Hsp90抑制劑的研究. 國外醫藥: 抗生素分冊, 2013, 34(4): 145-148.
5. 金正均. 合并用藥中的相加. 中國藥理學報, 1980, 1(2): 70-76.
6. 靳夢亞, 董玲, 戴俊東, 等. Bradford法測量不同加工工藝鹿茸蛋白含量研究. 中華中醫藥學刊, 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, 劉金彪, 侯永強, 等. 分化型甲狀腺癌組織中HSP70與TNF-α的表達及與臨床病理的相關性. 中國老年學雜志, 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. 陳強, 張其忠, 劉健, 等. 紫杉醇脂質體與傳統紫杉醇治療乳腺癌和非小細胞肺癌的隨機對照研究. 中華腫瘤雜志, 2003, 25(2): 190-192.
12. 楊振磊, 張四喜, 黃桂華, 等. 抗腫瘤藥紫杉醇載體的研究進展. 中國生化藥物雜志, 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, M?usbacher 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, 韓曉紅, 鄭翠玲, 等. ELISA檢測腫瘤患者熱休克蛋白90α的影響因素分析. 中華檢驗醫學雜志, 2013, 36(12): 1100-1103.
17. 朱奇, 祝宇, 徐云澤, 等. 熱休克蛋白抑制劑對嗜鉻細胞瘤裸鼠移植瘤的抑制作用. 國際泌尿系統雜志, 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. 趙學榮, 王建平, 肖麗君, 等. 17-AAG阻滯HCT-15細胞周期并誘導其凋亡. 中國病理生理雜志, 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. 陳愛華, 于皆平. 胰腺癌組織中Survivin和CasPase-3蛋白的表達與患者臨床病理特征及生存期的關系. 現代中西醫結合雜志, 2015, 24(15): 1625-1627.
23. 潘科, 盧書明, 于勁達, 等. 胃癌及癌前病變細胞凋亡與caspase9, Bax表達的關系. 現代腫瘤醫學, 2010, 18(2): 317-319.
24. 殷舞, 莫祥蘭, 韋海明, 等. Survivin、Apaf-1和caspase9在胃癌腹膜轉移中的表達及意義. 廣東醫學, 2014, 35(2): 221-223.
25. 金彬, 玄云澤, 李京旭, 等. 術前間質化療對口腔鱗狀細胞癌中Ki-67、Caspase-3蛋白的影響. 重慶醫學, 2014, 43(14): 1707-1709.
26. 艾毅欽, 汪勇, 趙川, 等. Caspase-9蛋白表達水平對預測直腸癌術前放化療敏感性的臨床意義. 昆明醫科大學學報, 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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