ABSTRACT
@#[Abstract] Objective: To construct and verify the anti-tumor activity of chimeric antigen receptor (CAR) modified NK-92 cells (CAR-NK-92 cells) targeting prostate stem cell antigen (PSCA) in cervical cancer. Methods: Lentiviral vector expressing CAR targeting PSCA was constructed, and PSCA CAR-NK-92 cells were obtained by lentivirus transfection. The expression of PSCA in human cervical cancer cells was determined by Flow cytometry and Western blotting. The killing effect of PSCA CAR-NK-92 cells against cervical cancer cells was verified by co-incubation of effector and target cells in vitro, and the tumor inhibitory ability of PSCA CAR-NK-92 cells was verified with the nude mice xenograft model in vivo. Results: PSCA CAR-NK-92 cells were successfully constructed. PSCA was highly expressed in human cervical cancer Hela and MS751 cells (all P<0.01). In vitro co-incubation results showed that PSCA CAR-NK-92 cells could lyse PSCA+ cervical cancer transplanted tumor in a dose-dependent manner. In vivo anti-tumor data showed that PSCA CAR-NK-92 cells significantly inhibited the growth of cervical cancer cells compared with NK-92 cells transfected with vehicle vectors (P<0.01). In addition, PSCA CAR-NK-92 cells could effectively infiltrate tumor tissues and promote the secretion of anti-tumor cytokines TNF-α and IFN-γ (all P<0.01). Conclusion: The CAR-NK-92 targeting PSCA shows good anti-tumor effect on PSCA+ tumor cells both in vitro and in vivo, and has potential to be a therapeutic strategy for cervical cancer.
ABSTRACT
Objective: To investigate the inhibitory effect of capsaicin on the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice and its possible molecular mechanism. Method: Transplanted tumor model of breast cancer MDA-MB-231 cells in nude mice were established. Then the tumor-bearing mice were randomly divided into 4 groups:model group, and low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1). Mice of low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1) were intraperitoneally injected with the corresponding dose of capsaicin, and the model group was injected with the same volume of phosphate buffer saline (PBS), once every 3 days, for a total of 8 times in succession. Body weight of mice and transplantation tumor volume were measured before each injection of capsaicin. Mice of each group were put to death 24 h after the last administration, and then the tumor volume, mass and the tumor inhibitory rate were calculated. The protein expression levels of high mobility group box 1 (HMGB1) and Toll-like receptors 4(TLR4) were measured by immunohistochemistry and Western blot. Result: No significant difference was observed between each group in body weight. However, compared with the model group, capsaicin (5, 10, 20 mg·kg-1) remarkably inhibited the tumor volume and mass (PPP-1) also markedly inhibited the protein expression levels of HMGB1 and TLR4 (PConclusion: Capsaicin remarkably inhibits the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice, and the possible mechanism may be related to the down-regulation of HMGB1 and TLR4 at the protein level.
ABSTRACT
Objective: To observe the inhibitory effect of astragalus polysaccharides (APS) on growth of human breast cancer MDA-MB-231 xenograft tumor in nude mice and its effect on the apoptosis of tumor cells, in order to study the effect of APS on growth and induction of apoptosis of triple negative breast cancer MDA-MB-231 and its possible molecular mechanism. Method: Human breast cancer cell MDA-MB-231 was inoculated into the right axillary subcutaneous of BALB/c-nu female nude mice to establish the transplanted tumor model of breast cancer. Eighteen nude mice were randomly divided into 3 groups:model group (saline per day), low-dose APS group (200 mg·kg-1 APS per day), and high-dose APS group (400 mg·kg-1 APS per day), with 6 rats in each group. The drug was administered by gavage (200 μL) daily for 21 days. In the experiment, the length and diameter of breast cancer transplanted tumor were measured every two days, and the tumor volume was recorded and calculated. At the end of the experiment, the changes of tumor mass and tumor volume of the low and high-dose APS groups and the model group were observed and compared, and the tumor inhibition rate was calculated. The cell morphology in tumor tissue was observed by hematoxylin-eosin (HE) staining, and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to verify the apoptosis of breast cancer tissues. The expressions of apoptosis-related proteins, such as B-cell lymphoma/leukemia-2 protein (Bcl-2), Bcl-2 associated X protein (Bax), Caspase in tumor tissues was detected by Western blot. Result: The tumor volume of breast cancer decreased in the low and high-dose APS groups, and the tumor inhibition rates were 37.9%and 57.57%, respectively, with statistically significant differences from the model group (PP0.01). HE of tumor tissue cells showed that APS led to obvious morphological changes, with apoptosis in the tissue cells. TUNEL staining showed that the apoptosis rate of tumor cells in APS intervention groups was higher than that in control group. Western blot showed that expression of Bcl-2 protein decreased(PPPPConclusion: APS can effectively inhibit the growth of MDA-MB-231 breast cancer xenografts in nude mice and induce apoptosis in human breast cancer MDA-MB-231 cells. The mechanism may be related to the effect of APS on expressions of apoptosis-related proteins Bcl-2, Bax, Caspase-9 and Caspase-7 in breast cancer cells.