Tomikawa M, Kubota T, Takahashi S, Matsuzaki S W, Kitajima M
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Anticancer Res. 1998 Mar-Apr;18(2A):1059-62.
Pancreatic cancer frequently recurs or metastasizes even after apparently curative surgical resection. Because of a low, five-year survival rate after radical surgery, multi-modal adjuvant treatment must be used to prevent recurrence of systemic spread.
The effectiveness of the experimental cancer chemotherapy of mitomycin C (MMC), cisplatin (DDP), doxorubicin (DXR) and 5-fluorouracil (5-FU) was evaluated in three human pancreatic cancer xenografts serially transplanted in nude mice.
When the effects of these agents were evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay, only MMC and DDP were effective on PAN-3-JCK, a poorly differentiated adenocarcinoma. When PAN-12-JCK, a moderately differentiated adenocarcinoma, was used an in vitro assessment of combined chemotherapy of MMC and DDP, a synergistic combination effect was observed. Three xenografts were transplanted subcutaneously into nude mice and the maximum tolerated doses of these agents were administered intraperitoneally or intravenously (DXR). MMC showed positive antitumor activity on PAN-3-JCK and PAN-12-JCK, and 5-FU was effective on PAN-12-JCK.
These results reflect the low sensitivity of clinical pancreatic cancer to conventionally available antitumor agents, and suggest the possible synergistic combination antitumor activity of MMC and DDP.
胰腺癌即使在看似根治性手术切除后仍经常复发或转移。由于根治性手术后五年生存率较低,必须采用多模式辅助治疗以防止全身扩散的复发。
在裸鼠中连续移植的三种人胰腺癌异种移植模型中评估了丝裂霉素C(MMC)、顺铂(DDP)、阿霉素(DXR)和5-氟尿嘧啶(5-FU)的实验性癌症化疗效果。
当通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H四唑溴盐(MTT)试验评估这些药物的效果时,只有MMC和DDP对低分化腺癌PAN-3-JCK有效。当使用中分化腺癌PAN-12-JCK进行MMC和DDP联合化疗的体外评估时,观察到协同联合效应。将三种异种移植模型皮下移植到裸鼠中,并通过腹腔内或静脉内(DXR)给予这些药物的最大耐受剂量。MMC对PAN-3-JCK和PAN-12-JCK显示出阳性抗肿瘤活性,5-FU对PAN-12-JCK有效。
这些结果反映了临床胰腺癌对传统可用抗肿瘤药物的低敏感性,并提示MMC和DDP可能具有协同联合抗肿瘤活性。