The Chinese medicine JC-001 enhances the chemosensitivity of Lewis lung tumors to cisplatin by modulating the immune response
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JC-001 is a Chinese medicine that can modulate the immunity in Hepa 1-6 tumor-bearing mice, and we questioned whether JC-001 can serve as efficient adjuvant chemotherapy. We aimed to identify a novel approach for enhancing cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy by immunomodulation. The anti-tumor activity in vitro was determined based on foci formation and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A LLC1 tumor xenograft model was used to analyze the activity of tumor rejection in vivo. The tumors were analyzed through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) staining and cytokine arrays. JC-001 suppressed foci formation and reduced the viability of Lewis lung carcinoma (LLC1) cells in vitro. JC-001 suppressed LLC1 tumor growth in immunodeficient BALB/c nude mice and in immunocompetent C57BL/6 mice to an even greater extent. Furthermore, JC-001 up-regulated interferon-γ expression in the tumor microenvironment, enhanced the Th1 response in tumor-bearing mice, and increased the chemosensitivity of LLC1 tumors to CDDP chemotherapy. The results of our study suggest that JC-001 is associated with low cytotoxicity and can significantly suppress tumor growth by enhancing the Th1 response. JC-001 is a Chinese medicine with potential clinical applications in CDDP-based chemotherapeutic regimens.Keywords:
Lewis lung carcinoma
MTT assay
Antitumor activity of Hypsizigus marmoreus, an edible mashroom, was investigated by in vivo bioassay. The aqueous extract, hereinafter referred to as YH, was tested against syngeneic tumor, Lewis lung carcinoma. YH was found to give a significant increase in life span when assayed using a solid tumor, Lewis lung carcinoma, by intraperitoneal administration, but not as much by oral administration. It was also found that YH have an inhibitory activity of spontaneous tumor metastasis in mice bearing Lewis lung carcinoma by intraperitoneal administration. YH significantly decreased the number of metastasized nodules. It was suggested by Winn test that antitumor and antimetasatic activities shown by YH was effective in increasing activity on immunological by competent cells.
Lewis lung carcinoma
Edible mushroom
Intraperitoneal injection
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Lewis lung carcinoma was found to cause hypercalcemia in tumor-bearing mice. 24R,25(OH)2D3 (K-DR, prepared by Kureha Chemical Ind.) significantly prolonged the survival time of mice with Lewis lung carcinoma. K-DR exhibited an antimetastatic effect on Lewis lung carcinoma, and also had an analgesic effect in mice with Lewis lung carcinoma.
Lewis lung carcinoma
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Object To investigate the effects of tetramethylpyrazine (TMP) and Danshen (DS) on the growth and metastasis of Lewis lung carcinoma and tumor angiogenesis. Methods C 57BL mice with Lewis lung carcinoma were used in this study, which were injected respectively with TMP injection 50, 100, and 200 mg/(kg·d) and DS injection 5, 10, and 20 g/(kg·d), ip, for 21 days. Then the volume, weight, and numbers of the metastatic foci on lungs, tumor microvessel density (MVD) were determined, the expression of vascular endothelial growth factor (VEGF) of Lewis lung carcinoma was observed. Results TMP could remarkably reduce the volume, weight, and numbers of the metastatic foci, MVD, and the expression of VEGF of Lewis lung carcinoma. But DS did not show remarkably effect on Lewis lung carcinoma. Conclusion TMP can remarkably inhibit the growth and metastasis of Lewis lung carcinoma on mice, and its mechanism might be relative to inhibiting the expression of VEGF and angiogenesis. DS injection has no remarkably effect on Lewis lung carcinoma.
Lewis lung carcinoma
Tetramethylpyrazine
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Changes in functional activity of phagocytes from blood and peritoneal fluid, and production of NO compounds nitrates and nitrites, were studied in mouse models of Lewis carcinoma of the lung and Ehrlich carcinoma of the lung. Growth of metastatic Lewis carcinoma of the lung was shown to be associated with inhibition of endogenic production of NO compounds and decreased spontaneous release of free oxygen radicals by blood neutrophils. Total amount of nitric compounds in urine from Lewis carcinoma-bearing mice was 22.5-70.7% lower than in the control. Concentration of nitric compounds as calculated for nitrates in tumor tissue varied from (2.83-5.16) 106 mol/kg tissue and was poorly associated with Lewis carcinoma stage. Significant decrease in spontaneous chemiluminescence of blood neutrophils associated with tumor growth was 36.8-87% for Lewis carcinoma and 44.7% for Ehrlich carcinoma. Spontaneous chemiluminescence of peritoneal macrophages and monocytes was similar to that in the control, while phagocyte-dependent chemiluminescence of stimulated cells rose 2.2to 4.5-fold (p
Lewis lung carcinoma
Phagocyte
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Bimolane (AT1727), 1,2-bis (4-morphplinomethy1-3,5-dioxopiperazinyl)-ethane, is a derivative of ICRF154. It was first synthesized by Shanghai Institute of Materia Medica, Chinese Academy of Sciences. It slightly inhibited tumor growth and markedly inhibited the spontaneous pulmonary metastases of Lewis lung carcinoma in C57BL/6 mice. Adenosine cyclic-3’, 5’-monophosphate (cAMP) was assayed by Camp-dependent protein kinase binding assay in tumor tissue and plasma. Bimolane elevated moderately the Camp levels in primary tumor tissue of Lewis lung carcinoma. The cAMP level of plasma in normal C57BL/6 mice was not significantly different from that in C57BL/6 mice bearing Lewis lung carcinoma. Bimolane did not change the cAMP levels of plasma in C57BL/6 mice bearing Lewis ling carcinoma.
Lewis lung carcinoma
Cyclic adenosine monophosphate
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Oxalysine was found to be an antitumor antibiotic with a simple chemical structure very similar to lysine. In this paper, the antimetastatic action of oxalysine was studied and compared with ICRF-159. The Lewis lung carcinoma-bearing mice were killed at intervals during 10-21 d after sc implantation of tumor. The lungs from these mice were transplanted to other mice to examine the presence of tumor cells by bioassay. On d 21 after implantation of lung the tumor growth was found in 78% of the recipient mice. Oxylysine(160 mg/kg/d) was injected ip for 10 d to the Lewis lung carcinoma-bearing mice. The antimetastatic action could be detected when the treatment was started on the next day after implantation of tumor cells(P<0.05).When the drug was started on d 8 after implantation, antimetastatic action was more marked with 17% incidence of lung metastases(P<0.01). Hence oxalysine possesses a definite antimetastatic effect on Lewis lung carcinoma.
Lewis lung carcinoma
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Objective To investigate the optimal method for synthesizing thiolated doxorubicin.Methods Thiolated doxorubicin was synthesized through two different methods.Doxorubicin was reacted with 2-iminothiolane(2-IT) and S-acetylthioglycolic acid N-hydroxysuccinimide ester(SATA),respectively.The synthesized thiolated doxorubicin was further characterized by HPLC and MSESI techniques.Several factors including molar ratios as well as reaction time were evaluated.Results The results showed that thiolated doxorubicin could be synthesized via both of the two methods successfully.Thiolated doxorubicin could be stable when doxorubicin was reacted with SATA.But the crude thiolated doxorubicin could be cyclized easily when doxorubicin was reacted with 2-IT.Conclusion Thiolated doxorubicin prepared with SATA is more feasible than that with 2-IT.
Molar ratio
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Lewis lung carcinoma
Solid tumor
Lung tumor
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Eosin
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OBJECTIVE: To study the killing effect of TRAIL combined with doxorubicin on osteosarcoma cells so as to explore the new method of clinical chemotherapy.METHODS:TRAIL and doxorubicin were used on the osteosarcoma cells respectively or jointly. The inhibition rate was measured by MTT assay. The apoptotic rate were analyzed with the flow cytometry. Changes of celluar ultrastructure were observed with a microscope. RESULTS:Twenty-four hours after the application of 50 ng/mL TRAIL and 5 μg/mL doxorubicin jointly on OS-732 cells, the inhibition rate was 85.47% which was significantly higher than that after the application of 50 ng/mL TRAIL (9.68%) and 5 μg/mL doxorubicin (18.41%) respectively,P0.01. Changes of celluar ultrastructure and apoptotic rate indicated apoptosis-inducing effect of joint application was much stronger than those of respective application.CONCLUSION: Combination of TRAIL and doxorubicin is obviously conducive to apoptosis of tumor cells.
MTT assay
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