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1.
Biomed Pharmacother ; 123: 109766, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31846841

RESUMO

OBJECTIVES: Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA). MATERIALS AND METHODS: The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells. RESULTS: The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of pericancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCA patients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells. CONCLUSIONS: DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCA patients. DPY30 might serve as a potential novel target for treatment of CCA patients.

2.
Oncol Lett ; 11(3): 2019-2026, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26998115

RESUMO

Natural killer (NK) cells have been demonstrated to inhibit tumor growth. However, the role of NK cells in the inhibition of hepatocellular carcinoma metastasis is not well understood. The present study aimed to investigate the roles that NK cells may serve in inhibiting hepatocellular carcinoma metastasis. The role of isolated NK cells in the inhibition, proliferation, migration and invasion of the hepatoma cell line, MHCC97-H, was examined in vitro. Additionally, the survival rate of NK cells labeled with carboxyfluorescein diacetate-succinimidyl ester was assessed in vivo. An orthotopic implantation model was used to evaluate the role of NK cells in suppressing MHCC97-H cells in vivo. The effect of interleukin (IL)-2 stimulation on the tumor-inhibitory role of the NK cells was measured indirectly by analyzing the expression of various NK cell receptors and activated NK cell markers. It was observed that the NK cells inhibited the proliferation, migration and invasion of the MHCC97-H cells in vitro. Furthermore, the NK cells demonstrated long-term survival in the livers of the nude mice, and inhibited lung metastasis of hepatocellular carcinoma in vivo. However, liver tumor growth was not inhibited by the NK cells. IL-2 was identified to enhance the tumor-inhibitory effect of NK cells. The present study concludes that IL-2 may enhance the antitumor activity of the NK cells, and thereby inhibit the metastases of hepatocellular carcinoma in mice.

3.
PLoS One ; 10(5): e0121538, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25933112

RESUMO

Cholangiocarcinoma (CCA), a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU) was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI) < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.


Assuntos
Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Capsaicina/uso terapêutico , Colangiocarcinoma/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Capsaicina/farmacologia , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos
4.
Zhonghua Gan Zang Bing Za Zhi ; 17(1): 53-8, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19203454

RESUMO

OBJECTIVE: To study the immunocharacteristics of bone marrow mesenchymal stem cell (MSC) and provide experimental evidence for the potential therapeutic application. METHODS: MSCs were isolated from rat bone marrow and confirmed by immunophenotype, and the growth dynamic and cell cycle were analyzed. MSCs were cultured with or without 200 U/ml interferon gamma (IFNg) , the expression of PDL-1, CD54, CD40, CD80, CD86, MHC-I, and MHC-II was detected by flow cytometry. MSCs were used as regulatory cells in mixed lymphocyte reaction (MLR), the PDL-1 and CD54 molecules on MSCs were blocked to explore their roles in MLR. The IFN, IL-2, IL-4 and IL-10 molecules in culture supernatant were quantified by ELISA. The homing of MSCs to liver and induction of microchimerism were analyzed after MSCs transplantation. RESULTS: The purity of MSCs was high. The growth curve showed that the first two days were the lag phase; the third, fourth, fifth days were the log phase; the sixth and seventh days were the stationary phase. Flow cytometry indicated that 76.0%+/-2.0% of the MSCs were in G1/G0 phase, 13.0%+/-2.0% in S phase, 10.0%+/-1.7% in G2 and M phase. IFNg treatment led to up-regulation of CD54, PDL-1, MHC-I and MHC-II, however, CD40, CD80 and CD86 were not expressed on MSCs even after IFNg treatment. MSCs inhibited MLR, IFNg treatment enhanced the inhibitory effect of MSCs on MLR. Blocking of PDL-1 or CD54 on MSCs partially alleviated the inhibition effect. There were high levels of IFNg and IL-10, and low level of IL-4 in the culture supernatant of MLR, however, IL-2 was not detected. MSCs can home to the liver and induce formation of microchimerism after transplantation. CONCLUSION: IFNg treatment enhances the inhibitory effect of MSCs on MLR, PDL-1 and CD54 are key molecules mediating this inhibitory effect. MSC can home to the liver and induce formation of microchimerism after transplantation.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Interferon gama/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Linfócitos T/imunologia , Animais , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Células da Medula Óssea/metabolismo , Proliferação de Células , Células Cultivadas , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Interferon gama/administração & dosagem , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Ratos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
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