The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs.
The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs.
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DOI：
10.3892/or.14.3.609
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发表时间：
2005-09
期刊：
影响因子：
4.2
通讯作者：
N. Matsuhashi;M. Saio;Atsushi Matsuo;Y. Sugiyama;S. Saji
中科院分区：
文献类型：
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作者：
N. Matsuhashi;M. Saio;Atsushi Matsuo;Y. Sugiyama;S. Saji
体内和体外临床研究表明，使用5-氟尿嘧啶（5-FU）和顺铂（CDDP）的组合具有显著的胃癌活性。此外，5-氟尿嘧啶与顺铂（FP治疗）的组合对胃癌具有协同细胞毒性。采用流式细胞术（FACS）和形态学观察两种胃癌细胞系对抗癌药物5-氟尿嘧啶（5-FU）和顺铂（CDDP）的敏感性。在形态学观察中，采用了一种新的实验技术，将癌细胞作为一层或两层细胞分布在薄的胶原凝胶中，并与抗癌药物一起培养。此后，将细胞用荧光Hoechst 33258（Ho）染色并拍照，然后用苏木精和伊红（H&E）染色并再次拍照。通过结合Ho-和H& E-染色的细胞的观察来确定细胞死亡模式。虽然5-FU和CDDP联合给药未诱导MKN-28（突变型p53）的凋亡，但在MKN 45（野生型p53）的情况下明显观察到凋亡细胞。CDDP作用3 h和5-FU作用21 h可诱导MKN 45细胞凋亡。这些结果表明，在癌细胞中的p53表达的类型可能是一个有前途的因素，在预测FP治疗的反应和管理CDDP之前，5-FU可能是更有效地诱导凋亡的胃癌细胞与野生型p53表达。这些结果可能为p53表达与胃癌细胞FP治疗的多药耐药（MDR）有关提供了证据。
Clinical in vivo and in vitro studies have revealed pronounced gastric cancer activity using the combination of 5-fluorouracil (5-FU) and cisplatin (CDDP). In addition, the combination of 5-fluorouracil plus cisplatin (FP treatment) possesses synergistic cytotoxicity against gastric cancer. Sensitivity of two gastric cancer cell lines to anti-cancer drugs, 5-fluorouracil (5-FU) and/or cisplatinum (CDDP), was evaluated by use of either flow cytometric analysis (FACS) or morphological observation in terms of induction of apoptosis. In morphological observation, a new experimental technique was used in which cancer cells were distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. Thereafter, cells were stained with fluorescent Hoechst 33258 (Ho) and photographed, then stained with hematoxylin and eosin (H&E) and photographed again. Cell death patterns were determined by combining observations of Ho- and H&E-stained cells. While combined administration of 5-FU and CDDP did not induce apoptosis of MKN-28 (mutant-type p53), apoptotic cells were markedly observed in the case of MKN45 (wild-type p53). In addition, consecutive administration of CDDP for 3 h and 5-FU for 21 h effectively induced apoptosis of MKN45. These results indicated that the type of p53 expression in cancer cells could be a promising factor in predicting response to FP therapy and the administration of CDDP prior to 5-FU may be more effective in inducing apoptosis of gastric cancer cells with wild-type p53 expression. These data may provide evidence to support the idea that p53 expression is related to multidrug resistance (MDR) in FP therapy of gastric cancer cell lines.