Chitnis M, Adwankar M
Tumori. 1986 Oct 31;72(5):469-73. doi: 10.1177/030089168607200503.
The in vitro effect of adriamycin (ADR) and lonidamine alone and in combination, at 37 degrees C and 43 degrees C, was investigated on murine leukemia P388 sensitive (P388/S) and resistant (P388/ADR) to adriamycin. The sensitive and the resistant cells were exposed in vitro with and without the drugs for 1 h at 37 degrees C and 43 degrees C. These cells were inoculated ip (10(6) cells/mouse) into groups of BDF1 mice. Cytotoxic effect of the treatment was assessed on the basis of percentage increase in life span (% ILS) of these animals, compared to the animals receiving cells which did not receive any treatment but exposed only to 37 degrees C for 1 h. It was observed that exposure of P388/ADR cells to lonidamine or adriamycin alone at 43 degrees C for 1 h resulted in greater cell kill, thus enhancing the % ILS of the experimental animals receiving those cells, compared to that of mice receiving the cells exposed to the same drugs for 1 h at 37 degrees C. However, the combination of lonidamine (0.02 mM) and adriamycin (10 micrograms/ml) at 43 degrees C for 1 h showed more than a synergistic effect, resulting in a % ILS of 120. Similar results were seen in the case of P388/S; however, the observations pertaining to P388/ADR are encouraging, since the mode of treatment has reversed the acquired resistance of P388 leukemia cells to adriamycin.
研究了阿霉素（ADR）和氯尼达明单独及联合使用在37℃和43℃时对阿霉素敏感（P388/S）和耐药（P388/ADR）的小鼠白血病细胞的体外作用。将敏感和耐药细胞在有或无药物的情况下于37℃和43℃体外暴露1小时。将这些细胞腹腔注射（10⁶个细胞/小鼠）到BDF1小鼠组中。根据这些动物的寿命延长百分比（%ILS）评估治疗的细胞毒性作用，并与接受未接受任何治疗但仅在37℃暴露1小时的细胞的动物进行比较。观察到，将P388/ADR细胞在43℃单独暴露于氯尼达明或阿霉素1小时导致更大的细胞杀伤，因此与接受在37℃暴露于相同药物1小时的细胞的小鼠相比，接受这些细胞的实验动物的%ILS有所提高。然而，氯尼达明（0.02 mM）和阿霉素（10微克/毫升）在43℃联合作用1小时显示出超过协同效应，导致%ILS达到120。在P388/S细胞中也观察到类似结果；然而，与P388/ADR相关的观察结果令人鼓舞，因为这种治疗方式逆转了P388白血病细胞对阿霉素的获得性耐药。
