Experimental study of thalidomide for treatment of murine hepatocellular carcinoma

Abstract

Abstract: Objective To study the therapeutic effect of thalidomide(Tha) on murine hepatocellular carcinoma. Methods In murine transplanted hepatoma model, thalidomide was administered intragastrically alone (200 mg/kg daily for 10 days) or in combination with doxorubicin. The antitumor activity of Tha was observed in solid and ascitic tumor models. Results Tha induced significant growth inhibition of solid hepatoma without obvious toxicity on peripheral blood cells and lymphocyte proliferation. Although Tha alone had no effect on the survival of mice with ascitic tumor, it showed a synergistic antitumor activity in combination with doxorubicin (Dox) in both solid and ascitic tumor models. Moreover, Tha reduced Dox-induced cytopenia and immunosuppression. Histological analysis of Tha-treated tumors revealed remarkably enhanced tumor necrosis and lymphocyte infiltration on the edge of tumor tissues. Conclusion Tha has definite therapeutic effect on murine hepatoma, and the combination with Dox shows an enhanced therapeutic potential.

CLC Number:

YANG Yi-ming¹, DU Gang-jun², LIN Hai-hong². Experimental study of thalidomide for treatment of murine hepatocellular carcinoma[J]. Journal of Southern Medical University, 2005, 25(08): 925-928.

References

[1] Bressoud A, Schwab BZ. Thalidomide: (re)discovery of a not very dear old molecule[J]. Rev Med Suisse Romande, 2003, 123 (4):238-40.
[2] Singhal S, Mehta J. Thalidomide in cancer[J]. Biomed Pharmacother, 2002, 56(1): 4-12.
[3] 翟羽,吕占军.反应停对小鼠肝癌细胞H22移植瘤生长的影响[J].癌症,2003,22(12):1301-6.Zhai Y.Lu ZJ.Effect of thalidomide on tumor growth in mouse hepatoma H22 model[J].Ai Zheng,2003,22(12):1301-6.
[4] 许启泰,杜钢军,陈百泉.美蓝的抗肿瘤作用[J].中国药理学通报,2002,18(3):352-3.Xu QT, Du GJ, Chen BQ. Antitumor action of methylene blue[J].Chin Pharmacol Bull, 2002, 18(3): 352-3.
[5] Myoung H, Hong SD, Kim YY, et al. Evaluation of the anti-tumor and anti-angiogenic effect of paclitaxel and thalidomide on the xenotransplanted oral squamous cell carcinoma[J]. Cancer Lett,2001, 163(2): 191-200.
[6] 杜钢军,林海红,许启泰托盘根提取物对不同细胞的影响[J].中国药科大学学报,2001,32(6):468-70.Du GJ, Lin HH, Xu QT. Effect of ethanol extract of roots of rubus crataegifolius on tumor cells[J]. J Chin Pharm Univ, 2001, 32(6):468-70.
[7] Raje N, Kenneth C. Thalidomide and immunomodulatory drugs as cancer therapy[J]. Oncology, 2002, 14(6): 635-40.
[8] D’Amato RJ, Loughman MS, Flynn E. Thalidomide is an inhibitor of angiogenesis[J]. Proc Natl Acad Sci USA, 1994, 91(9): 4082-5.
[9] 平宝红,陈琪,周淑云,等.反应停治疗老年难治性多发性骨髓瘤1例报告[J].第一军医大学学报,2002,22(10):954.Ping BH,Chen Q,Zhou SY,et al.Treatment of old refractory multiple myeloma withthalidomide:report of one case[J].J First Mil Med Univ/Di Yi Jun Yi Da Xue Xue Bao,2002,22(10):954.
[10] 杨义明,杜钢军,宋华勇,等沙利度胺治疗难治性多发性骨髓瘤的临床研究[J].临床荟萃,2005,20(2):97-8.Yang YM,Du GJ,Song HY,et al.Clinical study on thalidomide in multiple myeloma[J].Clin Focus,2005,20(2):97-8.
[11] 李峰敏,王玉荣,徐建民.反应停诱导骨髓瘤细胞株(KM3)凋亡的初步研究[J].中国临床医学,2002,9(1):9-11.Li FM, Wang YR, Xu JM. Induction of apoptosis by thalidomide in KM3 myeloma cell line[J]. Clin Med J Chin, 2002, 9(1): 9-11.
[12] Kenyon BM, Browne F, D’Amato RJ. Effects of thalidomide and related metabolites in a mouse comeal model of neovascularization[J]. Exp Eye Res, 1997, 64(6): 971-8.
[13] Rajkumar Sv, Fonseca R, Dispenzieri A, et al. Thalidomide in the treatment of relapsed multiple myeloma[J]. Mayo Clin Proc, 2000,75(9): 897-901.
[14] Karrow NA, Guo TL, Zhang LX, et al. Thalidomide modulation of the immune response in female B6C3F1 mice: a host resistance study[J]. Int Immunopharmacol, 2003, 3(10-11): 1447-56.
[15] 杨义明,杜钢军,林海红,等.反应停对HL-60细胞马利兰耐药的逆转作用[J].郑州大学学报(医学版),2005,40(2):300-2.Yang YM, -Du GJ, Lin HH, et al. Reverse effect of thalidomide on myleran-resistant HL-60 cells[J]. J Zhengzhou Univ (Med Sci),2005, 40(2): 300-2.
[16] Musto P. Thalidomide therapy for myelodysplastic syndromes: current status and future perspectives[J]. Leukemia Res, 2004, 28(4):325-32.