ABSTRACT
AIM:To investigate the mechanism of the radiosensitizing effect of maximum non-cytotoxic doses of tetrandrine (Tet) on nasopharyngeal carcinoma cell lines CNE1 and CNE2.METHODS:The cells were treated with maximum non-cytotoxic doses of Tet (for CNE1 cells at 1.5 μmol/L and for CNE2 cells at 1.8 μmol/L),irradiation at 4 Gy,or combination of irradiation and maximum non-cytotoxic doses of Tet.The cell cycle distribution was analyzed by flow cytometry.The protein levels of γ-H2AX,cleaved caspase-3,p-CDC25C,CDK1,p-CDK1,cyclin B1,ERK and p-ERK were determined by Western blot.RESULTS:The expression of γ-H2AX was increased in CNE1 cells and CNE2 cells after combined treatment with irradiation and maximum non-cytotoxic doses of Tet.The percentages of CNE1 cells and CNE2 cells at G2/M phase in irradiation group were (18.09 ±0.42)％ and (18.48 ± 1.32)％,respectively,which were decreased to (15.88 ± 1.04) ％ and (13.80 ± 0.82) ％ in combined treatment group,respectively (P ＜ 0.05).Combined treatment enhanced the increase in the protein level of cleaved caspase-3 caused by irradiation.The protein levels of pCDC25C and p-CDK1 were increased in a dose-dependent manner by Tet treatment (P ＜ 0.05),while the expression of CDK1 showed no difference among different doses of Tet treatments.The protein levels of p-CDC25C,p-CDK1 and CDK1 showed no difference after the treatment with maximum non-cytotoxic doses of Tet.The combined treatment with irradiation and the maximum non-cytotoxic doses of Tet decreased the protein levels of p-CDC25C and p-CDK1 (P ＜0.05),increased the expression of cyclin B1,and had no influence on the expression of CDK1 （ P ＜0.05).The combined treatment resulted in an increase in the protein level of p-ERK1 (P ＜ 0.05).CONCLUSION:The maximum non-cytotoxic doses of Tet enhance the DNA damage and apoptosis in CNE1 cells and CNE2 cells caused by irradiation,and the mechanism might be associated with ending of G2/M arrest via activation of ERK/CDC25C/CDK1/cyclin B1 pathways.
ABSTRACT
AIM:To investigate the mechanism of the radiosensitizing effect of maximum non-cytotoxic doses of tetrandrine (Tet) on nasopharyngeal carcinoma cell lines CNE1 and CNE2.METHODS:The cells were treated with maximum non-cytotoxic doses of Tet (for CNE1 cells at 1.5 μmol/L and for CNE2 cells at 1.8 μmol/L),irradiation at 4 Gy,or combination of irradiation and maximum non-cytotoxic doses of Tet.The cell cycle distribution was analyzed by flow cytometry.The protein levels of γ-H2AX,cleaved caspase-3,p-CDC25C,CDK1,p-CDK1,cyclin B1,ERK and p-ERK were determined by Western blot.RESULTS:The expression of γ-H2AX was increased in CNE1 cells and CNE2 cells after combined treatment with irradiation and maximum non-cytotoxic doses of Tet.The percentages of CNE1 cells and CNE2 cells at G2/M phase in irradiation group were (18.09 ±0.42)％ and (18.48 ± 1.32)％,respectively,which were decreased to (15.88 ± 1.04) ％ and (13.80 ± 0.82) ％ in combined treatment group,respectively (P ＜ 0.05).Combined treatment enhanced the increase in the protein level of cleaved caspase-3 caused by irradiation.The protein levels of pCDC25C and p-CDK1 were increased in a dose-dependent manner by Tet treatment (P ＜ 0.05),while the expression of CDK1 showed no difference among different doses of Tet treatments.The protein levels of p-CDC25C,p-CDK1 and CDK1 showed no difference after the treatment with maximum non-cytotoxic doses of Tet.The combined treatment with irradiation and the maximum non-cytotoxic doses of Tet decreased the protein levels of p-CDC25C and p-CDK1 (P ＜0.05),increased the expression of cyclin B1,and had no influence on the expression of CDK1 （ P ＜0.05).The combined treatment resulted in an increase in the protein level of p-ERK1 (P ＜ 0.05).CONCLUSION:The maximum non-cytotoxic doses of Tet enhance the DNA damage and apoptosis in CNE1 cells and CNE2 cells caused by irradiation,and the mechanism might be associated with ending of G2/M arrest via activation of ERK/CDC25C/CDK1/cyclin B1 pathways.
ABSTRACT
Objective To develop a musculoskeletal multi-body dynamic model of the patient-specific total knee replacement (TKR), and to simulate knee joint biomechanical characters of the patient during right-turn gait. Methods Based on the musculoskeletal dynamic software AnyBody and the method of force-dependent kinematics as well as the related data from a patient with TKR, the corresponding patient specific lower extremity musculoskeletal multi-body dynamic model was constructed and then used to simulate the right-turn gait of the patient. The knee contact forces, motion, muscle activations and ligament forces were predicted simultaneously by inverse dynamics analysis on such right-turn gait. ResultsThe root mean square error of the predicted average tibiofemoral medial contact force and lateral contact force were 285 N and 164 N, respectively, and the correlation coefficients were 0.95 and 0.61, respectively. The predicted average patellar contact force was 250 N. The predicted contact forces and muscle activations were consistent with those in vivo measurements obtained from the patient. In addition, the model also predicted the average range of tibiofemoral rotations of flexion-extension, internal-external, varus-valgus as 3°-47°, -3.4°-1.5°, 0.2°--1.5°, and the average range of tibiofemoral translations of anterior-posterior, inferior-superior, medial-lateral as 2.6-9 mm, 1.6-3.2 mm, 4.2-5.2 mm, respectively. The predicted average peak value of the medial, lateral collateral ligament force and posterior cruciate ligament force were 190, 108, 108 N, respectively. Conclusions The developed model can predict in vivo knee joint biomechanics, which offers a robust computational platform for future study on the failure mechanisms of knee prosthesis in clinic.