| Background and ObjectiveMelanoma is a kind of melanocytic or nevocytic malignant tumor, which was usually generate from cutaneous covering, and metastasize to other organs and mucous membrane by lymphatic and blood circulation. At present, Malignant melanoma respond poorly to treat with the tradition therapeutic regimen including exairesis,biotherapy,radiation and chemical therapy. There was no development about chemotherapecutive drugs which significant used for melanoma in recent years. Dacarbazine (DTIC ) and Cyclophosphamide (CTX) are the two most effective drug with the reaction rate of 20% and 16%. Such as DTIC and others, so it is of great to develop new therapeutic means for melanoma patients, especially for those resistant to conventional chemotherapecutive drugs. Arsenic trioxide has evident effect not only to treat leukemia but hepatoma,colon carcinoma,carcinoma of bladder, and some reports have confirmed arsenic trioxide can inhibit the growth of two types of melanoma cells A375 and B16.α-Interferon is very important cytogenic factor which is active to malignant melanoma. However, the reports about the effect of combining Interferon-awith arsenic trioxide treating malignant melanoma still have been seen.. In this study, we investigated the effect of As2O3 on melanoma established skin melanoma models and the possible mechanisms. Methods1. C57BL/6 mice bearing melanoma were divided into 5 groups at random:①As2O3 Group: Successive administration intraperitoneal injection of As2O3 10days,0.1mg/20g/d;②α-Interferon Group: Successive administration subcutaneous injectionα-Interferon 10days,50 thousand U/20g/d ;③Combination Group : Successive administration intraperitoneal injection of As2O3 and subcutaneous injectionα-Interferon 10days;④Positive control Group: Intraperitoneal injection of CTX 100mg/kg/d, only d1 administration ;⑤Negative control Group: Successive administration intraperitoneal injection of physiologic saline 10days.2.①To observe general state of evcry groups , measure size and weight of tumor and calculate the tumor inhibition rates;②To observe survival period of every groups;③HE staining analysis of the tumor tissue.Results1. The inhibitory action: The tumor weight of As2O3 Group, Combination Group,α-Interferon Group and CTX Group are 0.4055±0.1287g, 0.3756±0.1953g, 0.3756±0.1953g, 0.3435±0.0843g, and the tumor inhibition rates are 37.92%, 42.49%, 23.34%, 47.41%. As2O3 could obviously inhibit the growth of the melanoma lesions. There is significant difference between Combination Group andα-Interferon Group but no significant difference between any two groups of As2O3 Group, Combination Group and CTX Group.2. As2O3 could extend survival period of mice withα-Interferon, the survival period of with or withoutα-Interferon were 37.2±5.1d and 32.1±4.3d, respectively (P<0.05). The survival period ofα-Interferon Group, CTX Group and Negative control Group are 26.9±3.5d 29.0±3.9d and 23.1±3.6d.3. The solid tumor was globular nodosity-formed with the fish appearance on thecross section. The tumor body invaded extensively even made incursions into thebreast bone and collarbone, and the tumor volume of Negative control Group waslarger than other groups. The blood vessels of tumor in Negative control Group andCTX Group were less than other groups, and the tumor body in these two groups wassmaller and presented more regulated form. HE staining analysis of the tumor tissue showed a marked difference between the Negative control and As2O3 group, less cell number and dwindled or disappeared cells nuclear of melanoma of As2O3 Group and CTX Group by microscopy, presenting a typical differentiation shape, but there is no marked change betweenα-Interferon and Negative control group.Conclusion1. As2O3 can inhibit mouse melanoma growth in vivo.2. INF-αcan extend survival period of mice.3. As2O3 could inhibit mouse melanoma growth and extend survival period of mice withα-interferon obviously, and the mice showed a good tolerance.
|
PDF Full Text Request