1.Neuroprotective Effect of Baicalein on H_2O_2-induced PC12 Injury
China Pharmacy 2005;0(15):-
OBJECTIVE: To observe the neuroprotective effect of Baicalein on H2O2-induced PC12 injury.METHODS: The PC12 cells cultured in vitro were preincubated with BAI for 24 h before being duplicated into the irreversible oxidative damages model with 500 ?mol?L-1 H2O2,then the protective effect of BAI (BAI presence or withdrawal) on these damaged cells in vitro was observed. The cell activity was detected by MTT microcolorimetry, and the lactate dehydrogenase(LDH) level in supernatant was determined as well. RESULTS: After pretreatment with BAI for 24 h,the injury of PC12 cells was significantly lessened in the presence or withdrawal of drugs in modeling, especially in the presence of drugs. Microscopically, PC12 cells can be seen with fuzzy edge and increased size, and cell fusion occurred in the BAI-treated H2O2 injury model. Cell activity increased,LDH level in the medium decreased, which were significantly different as compared with the model group. CONCLUSION: BAI can significantly reduce the hypoxic-ischemic injury of PC12 cells. Its mechanism may be related to its ability in reducing the accumulation of free radicals induced by blockage of the respiratory chain, antioxidation and free radical scavenging.
2.Mechanisms of cancer treatment by radiotherapy combined with immune checkpoint blockade
Zehong CHEN ; Ruxiong SU ; Zike YANG ; Shijun KANG
Journal of International Oncology 2017;44(3):209-212
With the further researches on the immune mechanisms in tumor,more and more scholars notice the phenomenon that radiation activates the immunity,and find that radiotherapy causes immunity suppression is one-sided.Although body's anti-tumor immunity can be enhanced by radiotherapy,in clinical,we observe that patients who receive radiotherapy cannot avoid tumor recurrence and metastasis.Researches show that tumor microenvironment makes the immune checkpoint pathway abnormally activated.Therefore,the combination of radiotherapy and immune checkpoint inhibitor can change the tumor microenvironment,and can improve the therapeutic effect.
3.Soluble PD-1 over-expression enhances the anti-tumor effect of senescence tumor cell vaccine against breast cancer cell growth in tumor-bearing mice
Zehong CHEN ; Huiwen LIN ; Kang HU ; Ruxiong SU ; Nan LAI ; Zike YANG ; Shijun KANG
Journal of Southern Medical University 2018;38(1):20-26
Objective To investigate whether soluble PD-1 overexpression in 4T1 senescence tumor cells enhances the anti-tumor effect of senescence tumor cell vaccine (STCV) against breast tumor cells in a tumor-bearing mouse model. Methods 4T1 cells were treated with interferon-γ (IFN-γ) and the expression of PD-L1 was detected by flow cytometry. CCK8 assay was used to compare the cell proliferation activity between 4T1 cells and 4T1 cells infected by a lentiviral vector of sPD-1 (4T1/sPD-1 cells), and the expressions of sPD-1 mRNA and protein in 4T1/sPD-1 cells were detected using qPCR and Western blotting. The culture supernatant of 4T1/sPD-1 cells was added in 4T1 cells pre-treated with IFN-γ, and PD-1-positive 4T1 cells were detected with flow cytometry. Senescenceβ-galactosidase staining kit was used to detect the senescent 4T1 and 4T1/sPD-1 cells following exposure to X-ray radiation and Veliparib. Balb/c mice bearing subcutaneous 4T1 tumor xenografts were treated with injections of PBS, 4T1 STCV, or 4T1/sPD-1 STCV, and tumor growth was observed. Results Stimulation with IFN-γconcentration-dependently up-regulated PD-L1 expression by as much as (84.80 ± 1.03)% in 4T1 cells (P<0.001). sPD-1 overexpression in 4T1 cells did not significantly affect the cell proliferation. Treatment of 4T1 cells with 4T1/sPD-1 cell culture supernatant significantly increased the proportion of PD-1 + cells from (6.893 ± 0.271)% to (55.450 ± 0.555)% (P<0.001). X-ray irradiation combined with Veliparib caused obvious senescence in 4T1 and 4T1/sPD-1 cells. In the tumor-preventing experiment, tumor formation occurred in all the mice in PBS group;28.787%of the mice in 4T1 STCV group and 55.556%in 4T1/sPD-1 STCV group showed no tumor formation. In the tumor treatment experiment, tumor formation occurred in all the mice in PBS groups while in 4T1 STCV and 4T1/sPD-1 STCV groups, 11.111% and 38.89% of the mice were tumor-free during the observation period, respectively. Conclusions Senescence tumor cells vaccine has anti-tumor effect against breast cancer in mice, and sPD-1 over-expression can enhance this effect of the vaccine.
4.Soluble PD-1 over-expression enhances the anti-tumor effect of senescence tumor cell vaccine against breast cancer cell growth in tumor-bearing mice
Zehong CHEN ; Huiwen LIN ; Kang HU ; Ruxiong SU ; Nan LAI ; Zike YANG ; Shijun KANG
Journal of Southern Medical University 2018;38(1):20-26
Objective To investigate whether soluble PD-1 overexpression in 4T1 senescence tumor cells enhances the anti-tumor effect of senescence tumor cell vaccine (STCV) against breast tumor cells in a tumor-bearing mouse model. Methods 4T1 cells were treated with interferon-γ (IFN-γ) and the expression of PD-L1 was detected by flow cytometry. CCK8 assay was used to compare the cell proliferation activity between 4T1 cells and 4T1 cells infected by a lentiviral vector of sPD-1 (4T1/sPD-1 cells), and the expressions of sPD-1 mRNA and protein in 4T1/sPD-1 cells were detected using qPCR and Western blotting. The culture supernatant of 4T1/sPD-1 cells was added in 4T1 cells pre-treated with IFN-γ, and PD-1-positive 4T1 cells were detected with flow cytometry. Senescenceβ-galactosidase staining kit was used to detect the senescent 4T1 and 4T1/sPD-1 cells following exposure to X-ray radiation and Veliparib. Balb/c mice bearing subcutaneous 4T1 tumor xenografts were treated with injections of PBS, 4T1 STCV, or 4T1/sPD-1 STCV, and tumor growth was observed. Results Stimulation with IFN-γconcentration-dependently up-regulated PD-L1 expression by as much as (84.80 ± 1.03)% in 4T1 cells (P<0.001). sPD-1 overexpression in 4T1 cells did not significantly affect the cell proliferation. Treatment of 4T1 cells with 4T1/sPD-1 cell culture supernatant significantly increased the proportion of PD-1 + cells from (6.893 ± 0.271)% to (55.450 ± 0.555)% (P<0.001). X-ray irradiation combined with Veliparib caused obvious senescence in 4T1 and 4T1/sPD-1 cells. In the tumor-preventing experiment, tumor formation occurred in all the mice in PBS group;28.787%of the mice in 4T1 STCV group and 55.556%in 4T1/sPD-1 STCV group showed no tumor formation. In the tumor treatment experiment, tumor formation occurred in all the mice in PBS groups while in 4T1 STCV and 4T1/sPD-1 STCV groups, 11.111% and 38.89% of the mice were tumor-free during the observation period, respectively. Conclusions Senescence tumor cells vaccine has anti-tumor effect against breast cancer in mice, and sPD-1 over-expression can enhance this effect of the vaccine.