| [Objective] Differentiation therapy against tumor was initiated from experimental therapy on leukemia. The relevant studies on leukemia by Chen have been in the lead internationally. However, researcher on differentiation therapy against solid tumors have relatively fallen behind, which still concentrated mainly on in vitro studies. Our laboratory have already systemically observed the differentiation inducing effects of HMBA and DMIF on human glioma cell line SHG-44. On the basis of screening out another effective differentiation-inducer SPB on cell line SHG-44-9, we centred the experiments on differentiation inducing effects of SPB on transplanted solid tumor model, ie. Human glioma-bearing NC nude mice and SICD mice. Furthermore, BCNU and activated human lymphocytes have been applied together with SPB for the purpose of pursuing a new effective way for differentiation therapy against human glioma. [Method] 0 low differentiation degree human glioma cell line SHG-44-9 was inoculated subcutaneously on NIJ nude mice and SCID mice to create solid tumor model. IL-2 activated human peripheral lymphocytes (HuPBL) were transfused to SCID mice into create human-mouse immuno-chimeric model. ã’PB was applied alone, or combined with BCNU and HuPBL, to tumor-bearing mice (SPB 300 mg/kg, Bidx29d, BCNU 20 mg/kg Q4dx3, Iv HuPBL 1 x 10 ~ per mouse, once a week for two weeks).?Tumor size was measured, tumor cell cycle and expression of MI-IC-I and (3FAP were assayed by FCM, cell apoptosis was detected by TUNEL, c-myc protein was detected by Western blot .Pathological changes of transplanted tumors were observed under microscope. [Results] ?SPB therapy alone can obviously inhibit the growth of transplanted tumors. The inhibition rate was 67%, compared with the control group (P<0.0 1). The heteromorphism of tumor cells lowered under microscope, tumor cell proliferation arrested in S-phase proved by FCM. The expression level of GFAP and MHC-I increased as well. Tumor cells apoptosis obviously observed by TUNEL, c-myc protein expression lowered,all above resuts proved the differentiation-inducing effects of SPB on glioma cells in vivo. ?If combined with other therapies, namely, cytotoxic chemotherapeutic agent BCNU was applied for one course of treatment, then followed by SPB, the therapeutic effects of which is better than SPB alone. If further applied with immunotherapy (activated HuPBL), the effects were the best. In part of tumor-bearing SCID mice, tumor disappeared grossly, although remnant tumor cells can be found under microscope. [Conclusion] ?SPB can inhibit the cell proliferation of transplanted human glioma and induce tumor cells toward maturation . ?Remarkable anti-glioma effects were obtained if SPB therapy is combined with BCNU, V BCNU can strengthen the differentiation-inducing effect of SPB. ?It is the first time that differentiation therapy was combined with immunotherapy, and it is proved that HuPBL can further enhance the anti-glioma effects of SIPB in combination with BCNU. |
