ABSTRACT
Cryptotanshinone, a natural compound isolated from the roots of Salvia miltiorrhiza Bge (Danshen), has been found to induce cancer cells apoptosis and impair cell migration and invasion in various malignancies, but its antiproliferation and chemosensitization effects of Cryptotanshinone on tongue squamous cell carcinoma(TSCC)still remain fully elucidated. In this study, the effects of Cryptotanshinone on the proliferation, apoptosis and cell cycle of human TSCC cells, including CAL 27 and SCC 9 cells, were measured. The results demonstrated that Cryptotanshinone dose-dependently inhibited cell migration and proliferation, and induced apoptosis in TSCC cells. Mechanistic study revealed that Cryptotanshinone suppressed the expression of p-STAT3, Bcl-2, CDK2, Snail and MMP2, and induced the expression of E-cadherin, P53, P21 and ß-catenin. Furthermore, we found that the combination treatment of Cryptotanshinone and paclitaxel more effectively inhibited TSCC cell proliferation and migration, and induced apoptosis via the inhibition of STAT3 signaling pathway. In brief, we provided the new evidence that Cryptotanshinone could enhance the efficacy of paclitaxel on TSCC cells in vitro and demonstrated that STAT3 signaling pathway played an important role in Cryptotanshinone-induced anticancer effects in human TSCC.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/pathology , Janus Kinases/metabolism , Paclitaxel/pharmacology , Phenanthrenes/pharmacology , STAT3 Transcription Factor/metabolism , Tongue Neoplasms/pathology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Humans , Models, Biological , Neoplasm Invasiveness , Signal Transduction/drug effectsABSTRACT
AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel. METHODS: Immunoliposomal docetaxel was prepared by coupling monoclonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin. RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoli-posomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dose-dependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation, strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation, immunoliposomal docetaxel significantly increased the percentage of G(2)/M cells and induced apoptosis, but significantly decreased the percentage of cells in G(2)/G(1) and S phase by comparison with liposomal docetaxel. Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells. Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased. CONCLUSION: Immunoliposomal docetaxel is strongly effective for target radiosensitation in LoVo colon carcinoma cells, and may offer the potential to improve local radiotherapy.
