ABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of action of Zilongjin (ZLJ) in antagonizing multi-drug resistance (MDR) of tumor cells.</p><p><b>METHODS</b>MDR tumor cells, including human breast cancer cell line MCF-7 and MCF-7/DOX, and human oral epithelial cancer cells KB and KBV200, were treated with ZLJ. The inhibition of ZLJ on cell proliferation was determined with MTT assay; cell cycle and fluorescence dye Rhodamine 123 intensity were detected by flow cytometry; and the expression of related proteins was examined by Western blot.</p><p><b>RESULTS</b>IC50 values in MDR cells after ZLJ treatment were similar to those in sensitive cells; MDR cells showed no cross resistance to ZLJ. Flow cytometric analysis showed that the cell cycles of either sensitive or MDR cells were arrested at S phase after exposure to ZLJ. Using ZLJ singly showed a weak inhibition on MDR of MCF-7/ DOX and KBV200 cells, but when used in combining with doxorubicin or vincistine, it evidently increased their cytotoxicity. Expression of P-glycoprotein in MCF-7/DOX cells decreased after ZLJ treatment in a time-dependent manner. Western blot showed that ZLJ could cause the apoptosis marker protein PARP cleavage to initiate the apoptotic pathway.</p><p><b>CONCLUSIONS</b>The proliferation of tumor cells with MDR could be inhibited by ZLJ and they show no cross resistance to ZLJ. The inhibitory effect is related to the activation of apoptotic pathway and the decrease of P-glycoprotein expression.</p>
Subject(s)
Female , Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Breast Neoplasms , Pathology , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Drugs, Chinese Herbal , Pharmacology , MCF-7 Cells , Mouth Neoplasms , PathologyABSTRACT
Quorum sensing systems of pathogens are central regulators for the expression of virulence factors. Increasing evidence implies that targeting the quorum sensing system of many pathogenic bacteria is a promising therapeutic approach to control infections. In this work,we isolated 47 strains of actinomycetes from the mud sample of Jiaozhou Bay. Quorum sensing inhibitory activity was monitored by Chromobacterium violaceum CV026. As a result,the culture broth extract of actinomycetes WA-7 was found to have significant quorum sensing inhibitory activity. This strain was assigned to the genus Streptomyces based on its 16S rDNA sequence. Further investigation revealed that the extract could inhibit the quorum sensing-controlled violacein and proteases production of C. violaceum in a concentration-dependent manner.