Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.

作者: Ke-Qi Han

DOI: 10.3748/WJG.V13.I24.3374

关键词:

摘要: AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model human hepatocellular carcinoma nude mice. METHODS: BEL-7402 cells were inoculated to form subcutaneous tumors, implanted into liver establish models mice. Seventy-five animals randomized divided five groups (n = 15). Bufalin was injected intraperitoneally three at doses 1.5 mg/kg (BF1), 1 (BF2) 0.5 (BF3) for d 15-24, respectively. The NS group an equal volume saline as above adriamycin ADM a dose 8.0 15. Ten mice each killed 25 survival time calculated. We also observed morphologic alterations myocardium, brain, liver, kidney tissues by pathology electron microscopy, measured apoptotic rate TUNEL staining method, detected expression genes bcl-2 bax immunohistochemical RT-PCR tissues. RESULTS: volumes reduced significantly (35.21 ± 12.51 vs 170.39 25.29; 49.83 11.46 83.99 24.63 25.29, P < 0.01, respectively), times prolonged BF1-2 (31.8 4.2 23.4 2.1 29.4 3.4 2.1, 0.05, necrosis mainly severe or moderate degree BF1-2. No morphological changes tissues. Apoptotic characteristics could be seen positive rates protein 10.0%, 20.0%, 10.0% 20.0%; 90.0%, 80.0%, 40.0% 30.0%, Loss mRNA found density increased progressively with increase RT-PCR. CONCLUSION: has significant no marked toxicity able induce apoptosis transplanted cells. This may mediated via up-regulating gene bax, which involved its mechanism bufalin.

参考文章(18)
George G Chen, Paul BS Lai, Xu Hu, Isa KY Lam, Ernest CW Chak, Ying S Chun, Wan Y Lau, None, Negative correlation between the ratio of Bax to Bcl-2 and the size of tumor treated by culture supernatants from Kupffer cells. Clinical & Experimental Metastasis. ,vol. 19, pp. 457- 464 ,(2002) , 10.1023/A:1016336724463
Yutaka Masuda, Nobuko Kawazoe, Shigeo Nakajo, Takemi Yoshida, Yukio Kuroiwa, Kazuyasu Nakaya, Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells Leukemia Research. ,vol. 19, pp. 549- 556 ,(1995) , 10.1016/0145-2126(95)00031-I
F Pettersson, A G Dalgleish, R P Bissonnette, K W Colston, Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-γ and altered expression of Bcl-2/Bax British Journal of Cancer. ,vol. 87, pp. 555- 561 ,(2002) , 10.1038/SJ.BJC.6600496
Yongkui Jing, Hidekazu Ohizumi, Nobuko Kawazoe, Sachiko Hashimoto, Yutaka Masuda, Shigeo Nakajo, Takemi Yoshida, Yukio Kuroiwa, Kazuyasu Nakaya, Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells. Japanese Journal of Cancer Research. ,vol. 85, pp. 645- 651 ,(1994) , 10.1111/J.1349-7006.1994.TB02408.X
Mi-Hyeon Jang, Min-Chul Shin, Hye-Sook Shin, Khae-Hawn Kim, Heung-Jae Park, Ee-Hwa Kim, Chang-Ju Kim, Alcohol induces apoptosis in TM3 mouse Leydig cells via bax-dependent caspase-3 activation. European Journal of Pharmacology. ,vol. 449, pp. 39- 45 ,(2002) , 10.1016/S0014-2999(02)01973-8
Kazunari Yamada, Ken-ichiro Hino, Shigeru Tomoyasu, Yoshio Honma, Nobuyoshi Tsuruoka, Enhancement by bufalin of retinoic acid-induced differentiation of acute promyelocytic leukemia cells in primary culture. Leukemia Research. ,vol. 22, pp. 589- 595 ,(1998) , 10.1016/S0145-2126(98)00044-7
Masahiko Watabe, Yutaka Masuda, Shigeo Nakajo, Takemi Yoshida, Yukio Kuroiwa, Kazuyasu Nakaya, The Cooperative Interaction of Two Different Signaling Pathways in Response to Bufalin Induces Apoptosis in Human Leukemia U937 Cells Journal of Biological Chemistry. ,vol. 271, pp. 14067- 14073 ,(1996) , 10.1074/JBC.271.24.14067
Beatriz Bellosillo, Neus Villamor, Armando López-Guillermo, Silvia Marcé, Francesc Bosch, Elias Campo, Emili Montserrat, Dolors Colomer, Spontaneous and drug-induced apoptosis is mediated by conformational changes of Bax and Bak in B-cell chronic lymphocytic leukemia Blood. ,vol. 100, pp. 1810- 1816 ,(2002) , 10.1182/BLOOD-2001-12-0327
Wei-Kuo Chang, Kuender D. Yang, Hau Chuang, Jia-Tsong Jan, Men-Fang Shaio, Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Clinical Immunology. ,vol. 104, pp. 151- 160 ,(2002) , 10.1006/CLIM.2002.5257
Jiun-Yih Yeh, William J. Huang, Shu-Fen Kan, Paulus S. Wang, Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. The Prostate. ,vol. 54, pp. 112- 124 ,(2003) , 10.1002/PROS.10172