Effects of anti-cancer chemotherapy, anabolic hormone, cytokine an apoptosis

最近的体外研究表明，诱导细胞凋亡是化疗药物抗癌作用的重要机制。采用裸鼠移植的人胃肠道肿瘤异种移植物，研究了5-氟尿嘧啶（5-FU）和顺铂及其联合用药对人胸腺嘧啶合成酶、胸腺嘧啶合成酶的体内长期和短期影响及其抑制作用。先前建立的人胃癌（SC-1-NU）和结肠癌（Co-4）异种移植物皮下移植于雄性BALB/c裸鼠，用于实验性抗癌化疗方案。5-FU联合顺铂仅在SC-1-NU肿瘤短期治疗后才增加细胞凋亡。尽管给予5-FU显著增加胸腺苷酸合成酶抑制率，但无论肿瘤异种移植和治疗时间如何，额外剂量的顺铂并没有进一步增加胸腺苷酸合成酶抑制率。提示细胞凋亡在顺铂加5-FU的增强作用中起重要作用。5-FU与顺铂联用后胸腺苷合酶抑制未进一步升高，提示胸腺苷合酶抑制不是增强抗癌作用的主要机制。

In vitro study recently showed that induction of apoptosis is an important mechanism responsible for the anti-cancer effects of chemotherapeutic agents. In vivo long-term and short-term effects of 5-fluorouracil (5-FU) and cisplatin and their combination on papooses, thymidylate synthase and its inhibition were examined using human gastrointestinal cancer xenografts transplanted in nude mice. Previously established xenografts of human stomach carcinoma (SC-1-NU) and colon carcinoma (Co-4) subcutaneously transplanted in male BALB/c nude mice were used for the experimental anti-cancer chemotherapy regimen. The combination of 5-FU and cisplatin increased apoptosis only after the short-term treatment performed on SC-1-NU tumor. While administration of 5-FU markedly increased percent thymidylate inhibition rate, additional dose of cisplatin did not further increase the percent thymidylate synthase inhibition rate regardless of the tumor xenograft and the duration of the treatment. These results suggests that apoptosis play an important role in potentiating effect of cisplatin with 5-FU. No further increase in thymidylate synthase inhibition after the combination of 5-FU and cisplatin indicates that thymidylate synthase inhibition is not a major mechanism responsible for potentiating the anti0cancer effects.