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第十五届国际药理学大会

作者： Sheng- tao Yuan Tian-pa You Tao Wang .Zong-gui Wang Xin Fan Lu-yong Zhang.The Drag Screening Center.China Pharmaceutical University.Nanjing.Jiansu.China.University of Science and Technology of China.Hefei Anhui.China.

＜正＞ XY - 8 is a new water - solubility derivate from camptotecin. which,compared with camptotecin. appears to be less toxicity and more cytotoxic against human tumor cells. In this study,we report the anticancer activity of XY - 8 on 9 kinds of human tumor including lung carcinoma,stomach carcinoma （2 cell lines）. hepatocarcinoma（2 cell lines）,breast carcinoma,colon carcinoma,leukemia,cervix carcinoma,ovarian cancer and glioblastoma in vitro or in vivo. The average IC50 value of XY - 8 1.22 μM. In contrast,the average IC50 values of camptotecin were 10.54 μM. The LD50 was 280 mg/kg on mice by iv.. In nude mice,the T/C （ % ） were 44.2 at the dose of 2. 5mg/kg and 53.76 at the dose of 5mg/kg on A - 549 xenograft,the T/C （ % ） were 27.3 at the dose of 2. 5mg/kg and 36. 6 at the dose of 5mg/kg on BGC - 823 xenograft,the T/C （ % ） were 43.3 at the dose of 2. 5mg/kg and 48.9 at the dose of 5mg/kg on SGC - 7901 xenograft, . The results showed that XY - 8 had strong growth inhibition of human tumor in vitro and in vivo and may be useful in human tumor chemotherapy duo to its water - solubility and less toxicity.

关键词： anticancer activity camptotecin derivate in vivo

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Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB

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World Journal of Gastroenterology 2005年第40期11卷 6258-6261页

作者： Yukiko Saitou Katsuya Shiraki Takenari Yamanaka Kazumi Miyashita Tomoko Inoue Yutaka Yamanaka Yumi Yamaguchi Naoyuki Enokimura Norihiko Yamamoto Keiichi Itou Kazushi Sugimoto Takeshi Nakano First Department of Internal Medicine

AIM- To investigate the reduction of cell viability in human hepatocellular carcinoma （HCC） cell lines induced by inhibition of nuclear factor kB （NFkB）. METIIOI）S： HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNF（x and TNF-related apoptosis-inducing ligand （TRAIL） at the point of the reduction of cell viability by inhibiting NFkB. RESULTS： E3330 decreased NFKB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFa, Fas ligand, and E3330 increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability. CONCLUSION： Inhibition of NFd3 sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.

关键词： E3330 NFkB inhibitor Cytotoxicity TRAIL TNFa Fas ligand Doxorubicin camptotecin

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