| Summary: | 碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 103 === Quetiapine, an atypical antipsychotic, is widely used for the treatments of Schizophrenia and other psychosis. Quetiapine functions as the blockers of dopamine, serotonin and norepinephrine. Up to present, to our knowledge, there is no study has been reported about the therapeutic effects of quetiapine and its underlined mechanisms. Here the cytotoxicity and related mechanisms of quetiapine were investigated using colon, liver and lung cancer cell lines for in vitro study. For in vivo study, both CT26 murine colon carcinoma-bearing and Huh7 human hepatoma-bearing mouse models were established to explore the anticancer effects and underlying mechanisms of quetiapine.
Methods:
For in vitro study, the cell viabilities of CT26/NF-B-luc2 colorectal carcinoma cells, Huh7/NF-B-luc2 human hepatoma cells and human lung cancer cells A549, H1299 after various concentrations of quetiapine treatments were determined by MTT assay. The NF-B activities of CT26/NF-B-luc2 and Huh7/NF-B-luc2 cells were assessed by bioluminescent imaging (BLI) and electrophoresis mobility shift assay (EMSA). The expressions of NF-B-related proteins were assayed by Western blot. For in vivo study, therapeutic efficacy of quetiapine was evaluated with CT26 murine colon carcinoma-bearing and Huh7 human hepatoma-bearing mouse models. Tumor-bearing mice were treated with PBS (control), quetiapine (16 mg/kg/d) for 18 days. Tumor growth curve was determined from the tumor size measured with digital caliper. The mice were sacrificed on day 18 post treatment and tumors were removed for further assays. NF-B activity and the expressions of NF-B-related proteins were evaluated with EMSA and Western blot, respectively.
Results:
For in vitro study, the MTT results and BLI showed that quetiapine effectively suppressed the growth and NF-B activity of CT26/NF-B-luc2, Huh7/NF-B-luc2, A549 and H1299 cells, respectively. The expressions of NF-B related proteins of tumor cells were suppressed by quetiapine as shown with Western blot. For in vivo study, significant differences in tumor volumes were found in both CT26 and Huh7 tumor-bearing mice starting from day 8 and day 4, respectively, after the first dose of quetiapine. Mice were sacrificed on day 18 post treatments, and the tumors were subjected to the ex vivo studies. The results from EMSA and Western blotting showed that the NF-B activity and NF-B-related protein expressions were suppressed after quetiapine treatments in these two tumor-bearing mouse models.
Conclusion:
Quetiapine could inhibit the growth of murine colon carcinoma, human hepatoma and lung carcinoma. The underlying mechanism may be through the inhibition of the EGFR/NF-B pathway.
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