Effect and Mechanism of Hydroxyapatite Nanoparticle on Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Guanglian ¹ , YANG Zhiqi ² , SUN Zhengang ² , WANG Shuai ² , XIA Xigang. ²

1.Medical School of Yangtze University, Jingzhou 434020, Hubei Province, China;;
2.Department of General Surgery, Jingzhou Center Hospital, Jingzhou 434020, Hubei Province, China;

Corresponding?author：

Keywords：

Hepatoocellular carcinoma; Transcatheter arterial chemoembolization; Hydroxyapatite nanoparticle; Effect; Mechanism

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

ObjectiveTo explore the effect of hydroxyapatite nanoparticle (nHAP) on hepatocellular carcinoma (HCC) and its mechanisms. MethodsThe literatures about the effect of nHAP on HCC were reviewed and summarized. ResultsAs a new nanoparticle, nHAP could suppress the DNA synthesis and subsequent division and proliferation of HCC cells through the inhibition of proliferating cell nuclear antigen (PCNA) and telomerase gene expression and increase of intracellular Ca2+. Moreover, nHAP was able to suppress the differentiation and metastases of HCC cells through the effect on the expressions of Paxillin and P130cas and the decrease of expressions of multiple drug resistance gene protein, microvessel density, and vascular endothelial growth factor. Finally, nHAP induced the apoptosis of HCC tumor cells by the regulation of bcl-2 and bax protein expressions. The combined use of nHAP and chemoembolization drugs could enhance the efficacy, prolong drug duration and reduce toxicity. ConclusionnHAP can inhibit the division, proliferation, differentiation, and metastases, and promote the apoptosis of HCC cells and combined use with chemoembolization drugs can enhance the efficacy and reduce toxicity.

Citation： WANG Guanglian,YANG Zhiqi,SUN Zhengang,WANG Shuai,XIA Xigang.. Effect and Mechanism of Hydroxyapatite Nanoparticle on Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(9): 1017-1020. doi: Copy

1.	Hu J, Liu ZS, Tang SL, et al. Effect of hydroxyapatite nanoparticles on the growth and p53/cMyc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection [J]. World J Gastroenterol, 2007, 13(20): 27982802.
2.	Baumann S, Fas SC, Giaisi M, et al. Wogonin preferentially kills malignant lymphocytes and suppresses Tcell tumor growth by inducing PLC gamma1 and Ca2+dependent apoptosis [J]. Blood, 2008, 111(4): 23542363.
3.	Li G, Dong S, Qu J, et al. Synergism of hydroxyapatite nanoparticles and recombinant mutant human tumor necrosis factoralpha in chemotherapy of multidrug resistant hepatocellular carcinoma [J]. Liver Int, 2010, 30(4): 585592.
4.	關鍵, 胡道予, 孫振綱, 等. 經動脈灌注納米微粒治療兔肝VX2腫瘤的實驗研究 [J]. 放射學實踐, 2007, 22(8): 786789.
5.	Wang A, Yin H, Li D, et al. Effects of organic modifiers on the sizecontrolled synthesis of hydroxyapatite nanorods [J]. Appl Surf Sci, 2007, 253(6): 33113316.
6.	Wang A, Yin H, Li D, et al. Sizecontrolled synthesis of hydroxyapatite nanorods in the presence of organic modifiers [J]. Mater Lett, 2007, 61(10): 20842088.
7.	Saha SK, Banerjee A, Bancrjee, et al. Synthesis of nanocrystalline hydroxyapatite using surfactant template systems: Role of templates in controlling morphology [J]. Mater Sci Eng C, 2009, 29(7): 22942301.
8.	Salarian M, SolatiHashjin M, Shafiei SS, et al. Templatedirected hydrothermal synthesis of dandelionlike hydroxyapatite in the presence of cetyltrimethylammonium bromide and polyethylene glycol [J]. Ceram Int, 2009, 35(7): 25632569.
9.	Li Y, Tjandra W, Tam KC. Synthesis and characterization of nanoporous hydroxyapatite using cationic surfactants as templates [J]. Mater Res Bull, 2008, 43(89): 23182326.
10.	曹獻英, 李世普, 張然, 等. 羥基磷灰石納米粒子對人肝癌細胞增殖及細胞周期的作用研究 [J]. 腫瘤防治雜志, 2003, 10(3): 256258.
11.	Nurse P. A long twentieth century of the cell cycle and beyond [J]. Cell, 2000, 100(1): 7178.
12.	張傳海, 許戈良, 葛勇勝, 等. 亞砷酸對肝癌細胞增殖及PCNA, cMyc蛋白表達的影響 [J]. 第四軍醫大學學報, 2005, 26(14): 13031306.
13.	Suehiro T, Matsumata T, Itasaka H, et al. Clinicopathologic features and prognosis of resected hepatocellular carcinomas of varied sizes with special reference to proliferating cell nuclear antigen [J]. Cancer, 1995, 76(3): 399405.
14.	尹美珍, 李世普, 韓穎超. 羥基磷灰石納米粒子對肝癌細胞PCNA表達的影響 [J]. 武漢理工大學學報, 2007, 29(8): 5861.
15.	Kannan TP, Nik Ahmad Shah NL, Azlina A, et al. In vivo chromosome aberration test for hydroxyapetite in mice [J]. Med J Malaysia, 2004, 59(Suppl B): 115116.
16.	Itokazu M, Sugiyama T, Ohno T, et al. Development of porous apatite ceramic for local delivery of chemotherapeutic agents [J]. J Biomed Mater Res, 1998, 39(4): 536538.
17.	Benghuzzi H. Longterm sustained delivery of 3′azido2′, 3′dideoxythymidine in vivo by means of HA and TCP delivery devices [J]. Biomed Sci Instrum, 2000, 36: 343348.
18.	齊志濤, 曹獻英, 韓穎超, 等. 納米磷灰石對人肝癌細胞端粒酶基因表達的影響 [J]. 武漢理工大學學報, 2004, 26(7): 4648.
19.	王寧, 李玉, 劉潔. 肝癌患者多藥耐藥基因檢測及其對介入治療療效影響分析 [J]. 中國實驗診斷學, 2006, 10(6): 572575.
20.	何平, 李金龍, 陳勇, 等. 中晚期肝癌聯合介入治療175例報道 [J]. 中國普外基礎與臨床雜志, 2010, 17(6): 615617.
21.	Brábek J, Constancio SS, Siesser PF, et al. Crkassociated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRCtransformed cells [J]. Mol Cancer Res, 2005, 3(6): 307315.
22.	潘勝利, 陳孝平, 張萬廣, 等. Paxillin和p130Cas蛋白在肝癌中的表達及意義 [J]. 中華外科雜志, 2006, 44(23): 16481649.
23.	李高鵬, 陳孝平, 黃志勇, 等. 碘油羥基磷灰石納米粒對兔VX2肝腫瘤Paxillin和P130Cas表達的影響 [J]. 腹部外科, 2008, 21(3): 181183.
24.	王寧, 李玉, 劉潔. 肝癌患者多要耐藥基因檢測及其對介入治療療效影響分析 [J]. 中國實驗診斷學, 2006, 10(6): 572575.
25.	Uggla B, Sthl E, Wgster D, et al. BCRP mRNA expression v. clinical outcome in 40 adult AML patients [J]. Leuk Res, 2005, 29(2): 141146.
26.	Li G, Chen X, Wang Q, et al. The role of four multidurg resistance proteins in hepatocellular carcinoma multidrug resistance [J]. J Huazhong Univ Sci Technolog Med Sci, 2007, 27(2): 173175.
27.	葉露, 李高鵬, 宋建新, 等. 碘油羥基磷灰石納米粒對兔VX2肝腫瘤多藥耐藥相關蛋白表達的影響 [J]. 胃腸病學和肝病學雜志, 2010, 19(5): 437439.
28.	葉義標, 陳濤. 肝癌血管生成與抗血管生成治療的研究進展 [J]. 中國普外基礎與臨床雜志, 2009, 16(10): 861865.
29.	徐濤, 陳孝平, 郭永憲, 等. 納米材料碘油混懸液栓塞對肝腫瘤金屬蛋白酶表達的影響 [J]. 中華消化雜志, 2008, 28(5): 335336.
30.	徐濤, 陳孝平, 郭永憲, 等. 納米材料碘油混懸液栓塞后兔VX2腫瘤組織MT1MMP表達改變的意義 [J]. 中華外科雜志, 2008, 46(8): 606609.
31.	Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors [J]. Breast Cancer Res Treat, 1995, 36(2): 169180.
32.	孫振綱, 董勝利, 李高鵬, 等. 碘油羥基磷灰石納米粒對兔VX2肝腫瘤生長及血管新生的作用 [J]. 華中科技大學學報（醫學版）, 2009, 38(3): 325329.
33.	張艷玲, 梁后杰, 肖文華, 等. 細胞凋亡、PCNA、p53和Fas與肝細胞癌臨床病理特征關系的研究 [J]. 第三軍醫大學學報, 2004, 26(24): 21912193.
34.	羅佳濱, 魏鳳香, 孟祥才, 等. 羥基磷灰石納米粒子誘導肝癌SMMC7721細胞凋亡的研究 [J]. 中國老年學雜志, 2006, 26(1): 7981.
35.	Feng LF, Zhong M, Lei XY, et al. Bcl2 siRNA induced apoptosis and increased sensitivity to 5fluorouracil and HCPT in HepG2 cells [J]. J Drug Target, 2006, 14(1): 2126.
36.	Kanda T, Yokosuka C, Imazeki F, et al. Enhanced sensitivity of human hepatoma cells to 5fluorouracil by small interfering RNA targeting Bcl2 [J]. DNA Cell Biol, 2005, 24(12): 805809.
37.	魏鳳香, 張濤, 李紅枝, 等. 羥基磷灰石納米粒子誘導肝癌SMMC7721細胞凋亡后bcl2和bax表達的變化 [J]. 中國老年學雜志, 2008, 28(13): 12611263.

1. Hu J, Liu ZS, Tang SL, et al. Effect of hydroxyapatite nanoparticles on the growth and p53/cMyc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection [J]. World J Gastroenterol, 2007, 13(20): 27982802.
2. Baumann S, Fas SC, Giaisi M, et al. Wogonin preferentially kills malignant lymphocytes and suppresses Tcell tumor growth by inducing PLC gamma1 and Ca2+dependent apoptosis [J]. Blood, 2008, 111(4): 23542363.
3. Li G, Dong S, Qu J, et al. Synergism of hydroxyapatite nanoparticles and recombinant mutant human tumor necrosis factoralpha in chemotherapy of multidrug resistant hepatocellular carcinoma [J]. Liver Int, 2010, 30(4): 585592.
4. 關鍵, 胡道予, 孫振綱, 等. 經動脈灌注納米微粒治療兔肝VX2腫瘤的實驗研究 [J]. 放射學實踐, 2007, 22(8): 786789.
5. Wang A, Yin H, Li D, et al. Effects of organic modifiers on the sizecontrolled synthesis of hydroxyapatite nanorods [J]. Appl Surf Sci, 2007, 253(6): 33113316.
6. Wang A, Yin H, Li D, et al. Sizecontrolled synthesis of hydroxyapatite nanorods in the presence of organic modifiers [J]. Mater Lett, 2007, 61(10): 20842088.
7. Saha SK, Banerjee A, Bancrjee, et al. Synthesis of nanocrystalline hydroxyapatite using surfactant template systems: Role of templates in controlling morphology [J]. Mater Sci Eng C, 2009, 29(7): 22942301.
8. Salarian M, SolatiHashjin M, Shafiei SS, et al. Templatedirected hydrothermal synthesis of dandelionlike hydroxyapatite in the presence of cetyltrimethylammonium bromide and polyethylene glycol [J]. Ceram Int, 2009, 35(7): 25632569.
9. Li Y, Tjandra W, Tam KC. Synthesis and characterization of nanoporous hydroxyapatite using cationic surfactants as templates [J]. Mater Res Bull, 2008, 43(89): 23182326.
10. 曹獻英, 李世普, 張然, 等. 羥基磷灰石納米粒子對人肝癌細胞增殖及細胞周期的作用研究 [J]. 腫瘤防治雜志, 2003, 10(3): 256258.
11. Nurse P. A long twentieth century of the cell cycle and beyond [J]. Cell, 2000, 100(1): 7178.
12. 張傳海, 許戈良, 葛勇勝, 等. 亞砷酸對肝癌細胞增殖及PCNA, cMyc蛋白表達的影響 [J]. 第四軍醫大學學報, 2005, 26(14): 13031306.
13. Suehiro T, Matsumata T, Itasaka H, et al. Clinicopathologic features and prognosis of resected hepatocellular carcinomas of varied sizes with special reference to proliferating cell nuclear antigen [J]. Cancer, 1995, 76(3): 399405.
14. 尹美珍, 李世普, 韓穎超. 羥基磷灰石納米粒子對肝癌細胞PCNA表達的影響 [J]. 武漢理工大學學報, 2007, 29(8): 5861.
15. Kannan TP, Nik Ahmad Shah NL, Azlina A, et al. In vivo chromosome aberration test for hydroxyapetite in mice [J]. Med J Malaysia, 2004, 59(Suppl B): 115116.
16. Itokazu M, Sugiyama T, Ohno T, et al. Development of porous apatite ceramic for local delivery of chemotherapeutic agents [J]. J Biomed Mater Res, 1998, 39(4): 536538.
17. Benghuzzi H. Longterm sustained delivery of 3′azido2′, 3′dideoxythymidine in vivo by means of HA and TCP delivery devices [J]. Biomed Sci Instrum, 2000, 36: 343348.
18. 齊志濤, 曹獻英, 韓穎超, 等. 納米磷灰石對人肝癌細胞端粒酶基因表達的影響 [J]. 武漢理工大學學報, 2004, 26(7): 4648.
19. 王寧, 李玉, 劉潔. 肝癌患者多藥耐藥基因檢測及其對介入治療療效影響分析 [J]. 中國實驗診斷學, 2006, 10(6): 572575.
20. 何平, 李金龍, 陳勇, 等. 中晚期肝癌聯合介入治療175例報道 [J]. 中國普外基礎與臨床雜志, 2010, 17(6): 615617.
21. Brábek J, Constancio SS, Siesser PF, et al. Crkassociated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRCtransformed cells [J]. Mol Cancer Res, 2005, 3(6): 307315.
22. 潘勝利, 陳孝平, 張萬廣, 等. Paxillin和p130Cas蛋白在肝癌中的表達及意義 [J]. 中華外科雜志, 2006, 44(23): 16481649.
23. 李高鵬, 陳孝平, 黃志勇, 等. 碘油羥基磷灰石納米粒對兔VX2肝腫瘤Paxillin和P130Cas表達的影響 [J]. 腹部外科, 2008, 21(3): 181183.
24. 王寧, 李玉, 劉潔. 肝癌患者多要耐藥基因檢測及其對介入治療療效影響分析 [J]. 中國實驗診斷學, 2006, 10(6): 572575.
25. Uggla B, Sthl E, Wgster D, et al. BCRP mRNA expression v. clinical outcome in 40 adult AML patients [J]. Leuk Res, 2005, 29(2): 141146.
26. Li G, Chen X, Wang Q, et al. The role of four multidurg resistance proteins in hepatocellular carcinoma multidrug resistance [J]. J Huazhong Univ Sci Technolog Med Sci, 2007, 27(2): 173175.
27. 葉露, 李高鵬, 宋建新, 等. 碘油羥基磷灰石納米粒對兔VX2肝腫瘤多藥耐藥相關蛋白表達的影響 [J]. 胃腸病學和肝病學雜志, 2010, 19(5): 437439.
28. 葉義標, 陳濤. 肝癌血管生成與抗血管生成治療的研究進展 [J]. 中國普外基礎與臨床雜志, 2009, 16(10): 861865.
29. 徐濤, 陳孝平, 郭永憲, 等. 納米材料碘油混懸液栓塞對肝腫瘤金屬蛋白酶表達的影響 [J]. 中華消化雜志, 2008, 28(5): 335336.
30. 徐濤, 陳孝平, 郭永憲, 等. 納米材料碘油混懸液栓塞后兔VX2腫瘤組織MT1MMP表達改變的意義 [J]. 中華外科雜志, 2008, 46(8): 606609.
31. Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors [J]. Breast Cancer Res Treat, 1995, 36(2): 169180.
32. 孫振綱, 董勝利, 李高鵬, 等. 碘油羥基磷灰石納米粒對兔VX2肝腫瘤生長及血管新生的作用 [J]. 華中科技大學學報（醫學版）, 2009, 38(3): 325329.
33. 張艷玲, 梁后杰, 肖文華, 等. 細胞凋亡、PCNA、p53和Fas與肝細胞癌臨床病理特征關系的研究 [J]. 第三軍醫大學學報, 2004, 26(24): 21912193.
34. 羅佳濱, 魏鳳香, 孟祥才, 等. 羥基磷灰石納米粒子誘導肝癌SMMC7721細胞凋亡的研究 [J]. 中國老年學雜志, 2006, 26(1): 7981.
35. Feng LF, Zhong M, Lei XY, et al. Bcl2 siRNA induced apoptosis and increased sensitivity to 5fluorouracil and HCPT in HepG2 cells [J]. J Drug Target, 2006, 14(1): 2126.
36. Kanda T, Yokosuka C, Imazeki F, et al. Enhanced sensitivity of human hepatoma cells to 5fluorouracil by small interfering RNA targeting Bcl2 [J]. DNA Cell Biol, 2005, 24(12): 805809.
37. 魏鳳香, 張濤, 李紅枝, 等. 羥基磷灰石納米粒子誘導肝癌SMMC7721細胞凋亡后bcl2和bax表達的變化 [J]. 中國老年學雜志, 2008, 28(13): 12611263.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect and Mechanism of Hydroxyapatite Nanoparticle on Hepatocellular Carcinoma

Abstract Full text Figures/Tables Video References Cited by

Format

Content