Yamamoto S, Tanaka H, Namba M
Gan To Kagaku Ryoho. 1987 Mar;14(3 Pt 1):699-705.
Experiments were performed to ascertain whether or not the cytotoxic effects of various anticancer drugs on five human genitourinary malignant cell lines would be enhanced by recombinant gamma-type interferon. The cells used were as follows: HeLa cells from a uterine cervix cancer, HT-1376 and EJ cells from bladder cancers, ACHN cells from a renal cancer, and PC-3 cells from a prostatic cancer. The effects of the drugs were studied by colony formation assay. The following drugs were used: two metabolic antagonists. cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), three antibiotics: adriamycin (ADM), mitomycin C (MMC) and peplomycin (PEP), two alkylating agents: nimustine hydrochloride (ACNU) and melphalan, one vinca alkaloid: vincristine (VCR) and one other drug: cisplatin (CDDP). Interferon used was a preparation of recombinant gamma-type interferon. PEP showed synergistically enhanced cytotoxic effects on HeLa, EJ, HT-1376, and ACHN cells by concomitant application with gamma-IFN. Synergistic cytotoxicity was also detected against HeLa, EJ and ACHN by combined treatment with ADM and gamma-IFN. A similar enhanced cytotoxicity was demonstrated in HT-1376 and PC-3 by 5-FU treatment with gamma-IFN. MMC showed enhanced cytotoxicity only against ACHN cells in the presence of gamma-IFN. The cytotoxic effects of PEP on cells were increased by lower concentrations of gamma-IFN compared with those of other drugs. DNA, RNA and protein synthesis were examined in HeLa cells following combined exposure to PEP and gamma-IFN. The combined therapy was found to produce a specific decrease in DNA synthesis, while yielding no significant inhibition of intracellular RNA and protein synthesis.
进行了实验以确定重组γ型干扰素是否会增强各种抗癌药物对五种人类泌尿生殖系统恶性细胞系的细胞毒性作用。所用细胞如下：来自子宫颈癌的HeLa细胞、来自膀胱癌的HT - 1376和EJ细胞、来自肾癌的ACHN细胞以及来自前列腺癌的PC - 3细胞。通过集落形成试验研究药物的作用。使用了以下药物：两种代谢拮抗剂，阿糖胞苷（Ara - C）和5 - 氟尿嘧啶（5 - FU）；三种抗生素：阿霉素（ADM）、丝裂霉素C（MMC）和培洛霉素（PEP）；两种烷化剂：盐酸尼莫司汀（ACNU）和美法仑；一种长春花生物碱：长春新碱（VCR）以及另一种药物：顺铂（CDDP）。所用干扰素为重组γ型干扰素制剂。PEP与γ干扰素联合应用时，对HeLa、EJ、HT - 1376和ACHN细胞显示出协同增强的细胞毒性作用。ADM与γ干扰素联合治疗对HeLa、EJ和ACHN细胞也检测到协同细胞毒性。5 - FU与γ干扰素联合处理在HT - 1376和PC - 3细胞中显示出类似的增强细胞毒性。MMC仅在γ干扰素存在下对ACHN细胞显示出增强的细胞毒性。与其他药物相比，较低浓度的γ干扰素就能增强PEP对细胞的细胞毒性作用。在HeLa细胞中联合暴露于PEP和γ干扰素后，检测了DNA、RNA和蛋白质合成。发现联合治疗使DNA合成特异性降低，而对细胞内RNA和蛋白质合成没有显著抑制。
