博来霉素A6和平阳霉素抗大肠癌实验研究
Study on Antitumor Activity of Bleomycin A6 and Pingyangmycin against Colorectal Cancer
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摘要: 本研究应用体外细胞毒试验,小鼠结肠癌移植瘤及裸鼠移植人大肠癌模型,观察博来霉素A6(A6)和平阳霉素(PYM)对大肠癌的疗效。结果发现2种药物在体外对人大肠癌细胞有较强的活性。在1/9LD50等毒性剂量下,A6和PYM对小鼠结肠癌26皮下和盲肠移植瘤的生长有明显的抑制作用,2次实验结果:对小鼠结肠癌皮下移植瘤,A6的抑瘤率分别为87％和88％,PYM为86％和91％,丝裂霉素C(MMC)为64％和25％,5—氟脲嘧啶(5—FU)为45％和27％;对盲肠移植瘤,A6抑瘤率分别为99％和97％,PYM为100％和97％,MMC为77％和25％,5—FU均为44％。同样A6和PYM对裸鼠移植的人结肠癌HT－29的生长也有较强的抑制作用,A6对肿瘤生长的抑制率为82％,PYM为78％,MMC为53％,5—FU为12％。表明A6和PYM对小鼠结肠癌的裸鼠移植的人结肠癌的生长抑制作用均明显较MMC和5—FU为强,A6的作用似略较PYM为强,但二者间无明显差别;在抑制肿瘤生长的同时,A6和PYM还使肿瘤的组织学发生变化,肿瘤坏死明显增加和核分裂数减少。在治疗剂量下A6和PYM对带瘤小鼠和荷瘤裸鼠的骨髓有核细胞数均无明显影响。Abstract: Effect on antitumor activity of bleomycin A6 (A6)and pingyangmycin (PYM)against colorectal cancer was observed with human tumor cloning assay for sensitivity testing, transplantablemurine colon cancer 26 and human colon cancer HT-29 xenograftin nude mice.A6 and PYMshowed cytotoxicity for human colorectal cells.On the basis of equitoxic dose (l/gLD50),A6 andPYM exerted much stronger growth inhibition than mitomycin C(MMC) and 5-fluorouracil(5 FU) against murine colon cancer 26 both implanted subcutaneously and cecally.On subcutaneoustumor in duplicate experiments, the inhibition rates were 87% and 88%by A6, 97% and 91%byPYM, 64% and 25%byMMC, 46% and 27%bys-Fu.On cecaltrumor, the inhibition rates were99% and 97% by A6, 97%and 100% by PYM, 77% and 25% by MMC,44% by 5-Fu,respectively.At a 1/9LD50 equitoxic dose, A6 and PYM also exertedmuch stronger growth inhibitionagainst human colon cancer HT-29 xenograft in nude mice than MMC and 5-Fu.More extensive necrosis was found in tumors treated with A6 and PYM than those with MMC and 5 Fu.These observations indicate that A6 and PYM are potent antitumor agents against colorectalcancer.
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