Objective: Reversing effects of traditional Chinese medicines on colorectal tumor immunosuppressions of natural killer (NK) cell and T lymphocyte were analyzed to provide evidence on selecting medicines for patient...Objective: Reversing effects of traditional Chinese medicines on colorectal tumor immunosuppressions of natural killer (NK) cell and T lymphocyte were analyzed to provide evidence on selecting medicines for patients according to the differ- ent types of tumor immunosuppression. Methods: Six traditional Chinese medicines, including Arsenious acid (AS), Ligustra- zine hydrochloride (LHC), Astragalus mongholicus bge (AMB), Matrine N-oxide (MOX), Polyporus umbellatus polysaccharide (PUPS) and Artesunate (ART), were enrolled. The reversing effects on suppression of murine splenocyte transformation and NK killing activity were measured by 3-{4,5-dimethyl-2-thiazolyl}-2,5-diphenyl tetrazolium (MTT), and the effects on the suppressed expression of intefieukin 2 receptor a (IL-2R(I), CD3E*~,* and CD3~.-~* were detected by flow cytometry (FCM). The effects on immunosuppressive molecules were measured by enzyme linked immunosorbent assay (ELISA), including transforming growth factor ~1 (TGF-~I), vascular endothelial growth factor (VEGF), interleukin 4 (IL-4), IL-6, IL-10 and pros- taglandin (PG) E2. Results: (1) The reversing effects of AMB on the inhibition of NK killing and CD3 expression were the most significant; the effect of LHC on inhibition of CD3 expression was the strongest; the effects of AMB, PUPS and ART on inhibition of transformation were the greatest; and the effect of ART on inhibition of IL-2Ra expression was the strongest. (2) The correlated molecules of these medicines that exerted reversing effects on colorectal tumor immunosuppression were TGF-~I and IL-10. AMB had the highest down-regulating effect on the secretion of TGF-~I. AS and ART had the highest effects on IL-10. Conclusion: Reversing tumor immunosuppression through the down-regulation of immunosuppressive molecules is one of the novel antitumor mechanisms of traditional Chinese medicines. The clinical use of compounded prescriptions of ART combined with AMB and LHC should be considered to avoid the reduced treatment efficiency caused by tumor im- munosuppression.展开更多
AIM: To investigate the effect of bone marrow-derived monocytes transfected with RNA of CT-26 (a cell line of mouse colon carcinoma) on antitumor immunity. METHODS: Mouse bone marrow-derived monocytes were incubated w...AIM: To investigate the effect of bone marrow-derived monocytes transfected with RNA of CT-26 (a cell line of mouse colon carcinoma) on antitumor immunity. METHODS: Mouse bone marrow-derived monocytes were incubated with mouse granulocyte macrophage colony stimulating factor (mGM-CSF) in vitro, and the purity of monocytes was detected by flow cytometry. Total RNA of CT-26 was obtained by TRIzol's process, and monocytes were transfected by TransMessenger in vitro. The activity of cytotoxic T lymphocytes (CTL) in vivo was estimated by the modified lactate dehydrogenase (LDH) release assay. Changes of tumor size in mice and animal's survival time were observed in different groups. RESULTS: Monocytes from mouse bone marrow were successfully incubated, and the positive rate of CDllb was over 95%. Vaccination of the monocytes transfected with total RNA induced a high level of specific CTL activity in vivo, and made mice resistant to the subsequent challenge of parental tumor cells. In vivo effects induced by monocytes transfected with total RNA were stronger than those induced by monocytes pulsed with tumor cell lysates. CONCLUSION: Antigen presenting cells transfected with total RNA of CT-26 can present endogenous? tumor antigens, activate CTL, and effectively induce specific antitumor immunity.展开更多
基金Supported by grants from Hebei Province Nature Science Foundation(No. H2012509001)Hebei Province Science&Technology Supporting Foundation (No. 092061111D)
文摘Objective: Reversing effects of traditional Chinese medicines on colorectal tumor immunosuppressions of natural killer (NK) cell and T lymphocyte were analyzed to provide evidence on selecting medicines for patients according to the differ- ent types of tumor immunosuppression. Methods: Six traditional Chinese medicines, including Arsenious acid (AS), Ligustra- zine hydrochloride (LHC), Astragalus mongholicus bge (AMB), Matrine N-oxide (MOX), Polyporus umbellatus polysaccharide (PUPS) and Artesunate (ART), were enrolled. The reversing effects on suppression of murine splenocyte transformation and NK killing activity were measured by 3-{4,5-dimethyl-2-thiazolyl}-2,5-diphenyl tetrazolium (MTT), and the effects on the suppressed expression of intefieukin 2 receptor a (IL-2R(I), CD3E*~,* and CD3~.-~* were detected by flow cytometry (FCM). The effects on immunosuppressive molecules were measured by enzyme linked immunosorbent assay (ELISA), including transforming growth factor ~1 (TGF-~I), vascular endothelial growth factor (VEGF), interleukin 4 (IL-4), IL-6, IL-10 and pros- taglandin (PG) E2. Results: (1) The reversing effects of AMB on the inhibition of NK killing and CD3 expression were the most significant; the effect of LHC on inhibition of CD3 expression was the strongest; the effects of AMB, PUPS and ART on inhibition of transformation were the greatest; and the effect of ART on inhibition of IL-2Ra expression was the strongest. (2) The correlated molecules of these medicines that exerted reversing effects on colorectal tumor immunosuppression were TGF-~I and IL-10. AMB had the highest down-regulating effect on the secretion of TGF-~I. AS and ART had the highest effects on IL-10. Conclusion: Reversing tumor immunosuppression through the down-regulation of immunosuppressive molecules is one of the novel antitumor mechanisms of traditional Chinese medicines. The clinical use of compounded prescriptions of ART combined with AMB and LHC should be considered to avoid the reduced treatment efficiency caused by tumor im- munosuppression.
文摘AIM: To investigate the effect of bone marrow-derived monocytes transfected with RNA of CT-26 (a cell line of mouse colon carcinoma) on antitumor immunity. METHODS: Mouse bone marrow-derived monocytes were incubated with mouse granulocyte macrophage colony stimulating factor (mGM-CSF) in vitro, and the purity of monocytes was detected by flow cytometry. Total RNA of CT-26 was obtained by TRIzol's process, and monocytes were transfected by TransMessenger in vitro. The activity of cytotoxic T lymphocytes (CTL) in vivo was estimated by the modified lactate dehydrogenase (LDH) release assay. Changes of tumor size in mice and animal's survival time were observed in different groups. RESULTS: Monocytes from mouse bone marrow were successfully incubated, and the positive rate of CDllb was over 95%. Vaccination of the monocytes transfected with total RNA induced a high level of specific CTL activity in vivo, and made mice resistant to the subsequent challenge of parental tumor cells. In vivo effects induced by monocytes transfected with total RNA were stronger than those induced by monocytes pulsed with tumor cell lysates. CONCLUSION: Antigen presenting cells transfected with total RNA of CT-26 can present endogenous? tumor antigens, activate CTL, and effectively induce specific antitumor immunity.