An novel hematoporphyrin-anticancer drug conjugate for a therapy of lung metastasis of sarcoma.

1.大鼠骨肉瘤S-SLM植入：选择合适的肺转移灶，植入F344大鼠（雄性）皮下层。我们将大鼠分为5组，每组10只。血卟啉-丝裂霉素C缀合物的制备：在DCC和4-二甲氨基吡啶的作用下，通过脱水反应将血卟啉和丝裂霉素C偶联。实验组：每组单次静脉给药1)对照组：仅注射DMSO2)低MMC组：8.97 * 10 -8 mol MMC3)低Hp-MMC组：8.97 * 10 -8 mol Hp-MMC4) MMC组：8.97 * 10 -7 mol MMC5) Hp-MMC组：8.97 * 10 -7 mol Hp-MMC4。结果：1)生存率：低MMC组生存率最高（90%）。而低Hp-MMC组、MMC组、Hp-MMC组的生存率分别为50%、20%、70% （p<0.001）。2)肺转移结节数：低MMC组肺转移结节数最少，平均35个。而Low Hp-MMC组、MMC组、Hp-MMC组的结节数分别为120个、35个、80个。3)转移灶坏死率：低MMC组坏死率最高（55%）。而Low Hp-MMC组、MMC组、Hp-MMC组的坏死率分别为12%、12%、34%，差异有统计学意义（p<0.001） 5。结论：血卟啉-丝裂霉素C缀合物的抗肿瘤作用低于丝裂霉素C，但血卟啉-丝裂霉素C缀合物的副作用更容易被接受。因此，我们认为，如果建立更好的方案，血卟啉-丝裂霉素C缀合物应该是一种新的抗肿瘤化疗药物。

1.Implantation of rat osteosarcoma, S-SLM : A appropriate focus of lung metastasis was selected, and implanted into the subcutaneous layr of F344 rat (male). We divided the rats into 5 groups as described below, each group included 10 rats.2.Preparation of hematoporphyrin-mitomycin C conjugate : Hematoporphyrin and mitomycin c were conjugated by dehydrated reaction under the DCC and 4-dimethylaminopyridine.3.Experimental group : A single intravenous administration was performed ineach group1) Control : Only DMSO2) Low MMC group : 8.97 * 10 -8 mol MMC3) Low Hp-MMC group : 8.97 * 10 -8 mol Hp-MMC4) MMC group : 8.97 * 10 -7 mol MMC5) Hp-MMC group : 8.97 * 10 -7 mol Hp-MMC4. Results :1) Survival rate : Low MMC group showed best survival rate 90%). However, survival rate of Low Hp-MMC group, MMC group, Hp-MMC group, were 50%, 20%, and 70%, respectively (p<0.001).2) Number of metastatic lung nodule : Low MMC group showed lowest lung nodules (average : 35). However, number of nodules of Low Hp-MMC group, MMC group, Hp-MMC group, were 120,35, and 80, respectively.3) Necrosis ratio of metastatic foci : Low MMC group showed best necrosis ratio (55%). However, necrosis ratio of Low Hp-MMC group, MMC group, Hp-MMC group, were significantly lower, which were 12%, 12%, and 34%, respectively (p<0.001).5.Conclusion : Hematoporphyrin-mitomycin C conjugate showed a lower anti tumor effect than that of mitomucin C.Side effects of hematoporphyrin-mitomycin C conjugate, however, has been more acceptable. Therefore we believe that hematoporphyrin-mitomycin C conjugate should be a novel anti tumor chemotherapy agent, if a better protocol would be established.