[Induction of differentiation in testicular choriocarcinoma cells and its role in cancer therapy].
As an approach to develop a new therapeutic modality for testicular germ cell tumor, in vitro studies were performed to investigate the capacity of testicular choriocarcinoma cell line JHTK-1 to differentiate and to screen its differentiation inducing substances. We have found that dibutyryl cyclic adenosine monophosphate (DBcAMP) induces multiple phenotypic changes of JHTK-1 cells within 48hr, i.e., morphological alteration, enhancement of human chorionic gonadotropin (HCG) production, and inhibition of the cellular proliferation. Upon addition of 1 mM DBcAMP to the culture mediums, broad and elongated cells with cytoplasmic projections, increased secretion of HCG to the culture mediums more than 15-fold and increased number of HCG positive cells more than 10-fold in immuno-histochemical study, and inhibition of cell proliferation more than 50 percent were seen. The changes were dose dependent as to DBcAMP. These results indicate that DBcAMP induces the differentiation of testicular choriocarcinoma cells from dividing cytotrophoblastic cells to non-dividing end cells of syncytio-trophoblastic cells. Screening of differentiation inducing substances were carried out using an increase in HCG secretion/cell/48 hr as an indicator of JHTK-1 cell differentiation. The inducers were theophylline, sodium butyrate, N-butyrate, vitamin C, vinblastine, and actinomycin D. In conclusion external stimuli such as chemical substances can induce the differentiation of testicular choriocarcinoma cells, and inhibit their cellular proliferation as well. This finding will lead to a concept of "differentiation induction therapy" for testicular choriocarcinoma.
Yamazaki
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D003994:Bucladesine / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002822:Choriocarcinoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003994:Bucladesine