Aim Chronic myelogenous leukemia （CML） is a hematopoietic stem cell cancer caused by the Bcr-Abl tyrosine kinase which arises from Philadelphia chromosome （Ph） translocation. Imatinib showed potent antitumor effic...Aim Chronic myelogenous leukemia （CML） is a hematopoietic stem cell cancer caused by the Bcr-Abl tyrosine kinase which arises from Philadelphia chromosome （Ph） translocation. Imatinib showed potent antitumor efficacy on CML but caused resistance, therefore, other chemotherapeutic drugs for CML are expected. Phosphati-dylinositol 3-kinases （PI3Ks） are lipid kinases that preferentially phosphorylate phosphatidylinositol 4,5-bisphos- phate （PIP2） to generate phosphatidylinositol 3,4,5-trisphosphate （PIP3） which activates the downstream Akt and mammalian target of rapamycin （mTOR） , and therefore play important roles in controlling signal pathways involved in cell proliferation, etc. ZSTK474, a specific PI3K inhibitor, was reported to show potent antitumor efficacy on various solid tumors, while the anti｜eukemia effect was not yet reported. Herein, the effects of ZSTK474 on K562 CML cells as well as the adriamycin-resistant human leukemia cells （K562/ADR） are reported. Methods Cell proliferation inhibition was detected by MTT assay. Cell cycle was analyzed by FACS. The expression of cell cycle related molecules like p27 and p21 was detected by western blot and qRT-PCR. Synergistic effect of ZSTK474 and Imatinib was evaluated by MTT assay and analyzed using Calcusyn. Results MTT assay showed that ZSTK474 could inhibit the proliferation of K562 and K562/ADR cells with ICs0 as 4 69 μmol · L^-1 and 7 57 μmol·L^-1 re- spectively. ZSTK474 induced cell cycle G1 arrest in the above two cell lines dose-dependently after 48 h treatment. Western blot analysis demonstrated ZSTK474 treatment decreased the level of cyclin D1 and increased the expres- sion of p27 and p21. Similar results in mRNA level were obtained by qRT-PCR assay. Combination of ZSTK474 and Imatinib indicated synergistic effect in both cell lines. Conclusion ZSTK474 exhibited anti-leukemia activity alone, and showed synergistic effect when combined with Imatinib, on CML K562 cells. These findings suggest possible application of ZSTK474 in CML treatment.展开更多
Background: Breast cancer is the most prevalent cancer and results in 14% of cancer-related deaths among women worldwide. The aim of this study is to investigate the anticancer effects of Silymarin on two breast cance...Background: Breast cancer is the most prevalent cancer and results in 14% of cancer-related deaths among women worldwide. The aim of this study is to investigate the anticancer effects of Silymarin on two breast cancer cell lines (BT-474, SK-BR-3). Methods and Material: Two breast cancer cell lines—SK-BR-3 and BT-474—were incubated for 24 hours in standard conditions before adding 100, 200, 400, 800, 1600 μM Silymarin to each well. Alamar blue was then added to the wells after 24, 48 and 72 hours of incubation and cell viability was determined using fluorescence reader to detect the optical density. Results were analyzed using generalized estimating equations (GEE) method in STATA 12.0. Results: we demonstrated the?Silybum marianum?inhibition of two-cell lines SK-BR-3 and BT-474 growth at different concentrations after 24, 48 and 72 hours. Silymarin increased cell death in both cell lines. Conclusion: Silymarin can be combined with other anti-neoplastic agents to obtain better results.展开更多
文摘Aim Chronic myelogenous leukemia （CML） is a hematopoietic stem cell cancer caused by the Bcr-Abl tyrosine kinase which arises from Philadelphia chromosome （Ph） translocation. Imatinib showed potent antitumor efficacy on CML but caused resistance, therefore, other chemotherapeutic drugs for CML are expected. Phosphati-dylinositol 3-kinases （PI3Ks） are lipid kinases that preferentially phosphorylate phosphatidylinositol 4,5-bisphos- phate （PIP2） to generate phosphatidylinositol 3,4,5-trisphosphate （PIP3） which activates the downstream Akt and mammalian target of rapamycin （mTOR） , and therefore play important roles in controlling signal pathways involved in cell proliferation, etc. ZSTK474, a specific PI3K inhibitor, was reported to show potent antitumor efficacy on various solid tumors, while the anti｜eukemia effect was not yet reported. Herein, the effects of ZSTK474 on K562 CML cells as well as the adriamycin-resistant human leukemia cells （K562/ADR） are reported. Methods Cell proliferation inhibition was detected by MTT assay. Cell cycle was analyzed by FACS. The expression of cell cycle related molecules like p27 and p21 was detected by western blot and qRT-PCR. Synergistic effect of ZSTK474 and Imatinib was evaluated by MTT assay and analyzed using Calcusyn. Results MTT assay showed that ZSTK474 could inhibit the proliferation of K562 and K562/ADR cells with ICs0 as 4 69 μmol · L^-1 and 7 57 μmol·L^-1 re- spectively. ZSTK474 induced cell cycle G1 arrest in the above two cell lines dose-dependently after 48 h treatment. Western blot analysis demonstrated ZSTK474 treatment decreased the level of cyclin D1 and increased the expres- sion of p27 and p21. Similar results in mRNA level were obtained by qRT-PCR assay. Combination of ZSTK474 and Imatinib indicated synergistic effect in both cell lines. Conclusion ZSTK474 exhibited anti-leukemia activity alone, and showed synergistic effect when combined with Imatinib, on CML K562 cells. These findings suggest possible application of ZSTK474 in CML treatment.
文摘Background: Breast cancer is the most prevalent cancer and results in 14% of cancer-related deaths among women worldwide. The aim of this study is to investigate the anticancer effects of Silymarin on two breast cancer cell lines (BT-474, SK-BR-3). Methods and Material: Two breast cancer cell lines—SK-BR-3 and BT-474—were incubated for 24 hours in standard conditions before adding 100, 200, 400, 800, 1600 μM Silymarin to each well. Alamar blue was then added to the wells after 24, 48 and 72 hours of incubation and cell viability was determined using fluorescence reader to detect the optical density. Results were analyzed using generalized estimating equations (GEE) method in STATA 12.0. Results: we demonstrated the?Silybum marianum?inhibition of two-cell lines SK-BR-3 and BT-474 growth at different concentrations after 24, 48 and 72 hours. Silymarin increased cell death in both cell lines. Conclusion: Silymarin can be combined with other anti-neoplastic agents to obtain better results.
