Akimoto M, Ueki H, Nakajima Y, Matano S, Ewasaki H, Abe R, Kasai M
Gan To Kagaku Ryoho. 1984 Jul;11(7):1462-7.
It is well known that all cell lines, normal as well as malignant, have a sensitivity to the growth-inhibitory effect of Interferon, or Interferon inducers. 5-FU is a widely used anticancer drug considered to be a cell cycle-specific agent. We speculated that the antiproliferative effect of Interferon or Interferon inducers might affect the activity of 5-FU and diminish the uncomfortable side-effects of this agent. Initially this experiment, we observed the mortality rate in mice after administration of 5-FU alone, or 5-FU plus Interferon (alpha inducers). We then carried out cytofluorometric observation of bone marrow cells, and finally studied the influence of Interferon (or inducers) on the anticancer effects of 5-FU against MM48 tumors in C3/He mice. Findings were as follow: 1) Administration of beta-type Interferon for 2 days, following the administration of a toxic dose (140 mg/kg/w) of 5-FU, revealed significant protection from mortality in C3H/He mice. This effect was also observed when Interferon inducers (Poly I: C, OK-432, Lentinan) were administered with 5-FU. Body weight loss was 10.4% at nadir in mice treated with 5-FU alone, while there was a body weight gain of 36.3% in mice treated with 5-FU plus Interferon. 2) Cytofluorometry of bone marrow cells obtained from mice femur at timed intervals after the administration of OK-432, or Lentinan indicated that these drugs inhibited the entry of cells into the S-phase, causing then to accumulated in the G0.G1-phase during the first 48 hours. 3) Histological findings of intestinal mucosa in mice showed prominent destruction after bolus injection of 350 mg/kg of 5-FU alone, while these findings were not observed in mice after the bolus injection of 350 mg/kg of 5-FU combined with Interferon. 4) The tumor volume ratio (T/C) was significantly reduced in the group treated with 5-FU alone as well as that treated with 5-FU combined with Interferon (or inducers) in C3H/He mice bearing MM48 tumors. All mice were dead about 2 weeks after administration of 5-FU alone, while all mice treated with 5-FU plus Interferon (or inducers) were alive in the same period. From these results, we speculate that Interferon, or Interferon inducers play an important role in the prevention of side effects of cell cycle-specific cytotoxic drugs like 5-FU, without decreasing their anticancer activity.
众所周知，所有细胞系，无论是正常的还是恶性的，对干扰素或干扰素诱导剂的生长抑制作用都具有敏感性。5-氟尿嘧啶（5-FU）是一种广泛使用的抗癌药物，被认为是一种细胞周期特异性药物。我们推测，干扰素或干扰素诱导剂的抗增殖作用可能会影响5-FU的活性，并减轻该药物令人不适的副作用。在本实验中，我们首先观察了单独给予5-FU或5-FU加干扰素（α诱导剂）后小鼠的死亡率。然后，我们对骨髓细胞进行了细胞荧光分析，最后研究了干扰素（或诱导剂）对5-FU抗C3/He小鼠MM48肿瘤的抗癌作用的影响。结果如下：1）在给予毒性剂量（140mg/kg/周）的5-FU后，连续2天给予β型干扰素，可显著保护C3H/He小鼠免于死亡。当干扰素诱导剂（聚肌胞苷酸：C、溶链菌制剂、香菇多糖）与5-FU联合使用时，也观察到了这种效果。单独用5-FU治疗的小鼠在体重最低点时体重减轻了10.4%，而用5-FU加干扰素治疗的小鼠体重增加了36.3%。2）在给予溶链菌制剂或香菇多糖后的不同时间间隔，对从小鼠股骨获得的骨髓细胞进行细胞荧光分析表明，这些药物抑制细胞进入S期，导致其在最初48小时内积聚在G0/G1期。3）小鼠肠道黏膜的组织学检查结果显示，单独推注350mg/kg的5-FU后，肠道黏膜有明显破坏，而在推注350mg/kg的5-FU与干扰素联合使用后的小鼠中未观察到这些结果。4）在携带MM48肿瘤的C3H/He小鼠中，单独用5-FU治疗的组以及用5-FU与干扰素（或诱导剂）联合治疗的组的肿瘤体积比（T/C）均显著降低。单独给予5-FU后约2周所有小鼠均死亡，而在同一时期，所有用5-FU加干扰素（或诱导剂）治疗的小鼠均存活。从这些结果中，我们推测干扰素或干扰素诱导剂在预防像5-FU这样的细胞周期特异性细胞毒性药物的副作用方面发挥着重要作用，同时不会降低其抗癌活性。
