时晓鑫
阜外华中心血管病医院 健康管理科
Colon cancer is a serious malignant type of cancer in the world. Acquisition of multi-drug resistance (MDR) during chemotherapy is still a controversial challenge during cancer treatment. Accordingly, detection of safe and impressive MDR-reversing targets such as microRNAs (miRNAs/miRs) can play critical role in cancer treatment. Here, the functional effects of miR-29a in chemo-resistant colon cancer cells is scrutinized. The effect of doxorubicin (DOX) on cell proliferation after miR-29a transfection has been evaluated using MTT assay in HT29 and HT29/DOX cells. Rhodamine123 (Rh123) assay is used to identify the activity of common drug efflux through membrane transporters P-glycoprotein (P-gp). P-gp and PTEN mRNA/protein expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Flow cytometry was employed to the investigation of apoptosis. ANOVA followed by Bonferroni's and Sidak's tests were used to compare the data from different groups. Thus, it was shown that miRNA-29a overexpression considerably inhibited the HT29/DOX viability. miR-29a significantly down-regulated P-gp expression and activity in HT29/DOX cells and declined drug resistance through elevation of intracellular DOX. Furthermore, upon miRNA-29a transfection, PTEN expression could be restored in resistant cells. These results have indicated that miR-29a target PTEN ultimately P-gp, which is downstream of PTEN, inhibit drug resistance, proliferation, and apoptosis through PI3K/Akt pathway. As a result, miR-29a overexpression is led to enhance the sensitivity of HT29/DOX cells to DOX-treatment by targeting P-gp. MiR-29a might proffer a novel promising candidate for colon cancer therapeutics during chemotherapy.
European journal of pharmacology 2020
Methicillin-resistant Staphylococcus aureus (MRSA) is an extensive origin of nosocomial infections that are very much challenging as well as complicated to eradicate mostly due to their strong resistance against all existing antibiotic therapies. Here the chitosan-grafted-polycaprolactone/maleic anhydride-pyrazinamide (CS-g-PCL/MA-PZA) polymeric drug carrier constructed via dialysis for anti-MRSA drugs like rifampicin (RF) and pyrazinamide (PZA) delivery. Nearly 200 nm size of the spherical particle with -20.04 mV of zeta potential observed. The cumulative PZA and RF releases from the carrier were observed 83.25% and 76.54% respectively in pH 5.5, and the in vitro drug release profile demonstrates that the fabricated micelle was pH-responsive. For the intestinal colonization, an in vivo assay performed using C. elegans, and the CS-g-PCL/MA-PZA/RF micelles treated worms generally belong to the weakly colonized category. Therefore, the study revealed that CS-g-PCL/MA-PZA/RF micelle could be a promising approach for therapeutic applications to achieve efficient anti-MRSA drug delivery.
International journal of biological macromolecules 2020
PURPOSE:To investigate the effect of miR-107 on the growth and metastasis of gastric cancer (GC) and elucidate the probable mechanisms.METHODS:The expression of miR-107 and FAT4 in GC tissues and cells were detected using qRT-PCR. Bioinformatics and dual luciferase reporter gene assays were used to analyze the relationship between miR-107 and FAT4. miR-NC, miR-107 inhibitor, pcDNA3.1-FAT4 and siRNA-FAT4 were transfected into AGS and MKN-45 GC cell lines, respectively. The proliferation and migration abilities of GC cells after transfection were evaluated using the MTT assay, scratch test and transwell assay. The expression of epithelial-mesenchymal transition (EMT) markers: E-cadherin, N-cadherin, vimentin and related proteins of the PI3K/AKT signaling pathway were determined using western blot. The xenograft tumors of nude mice were observed to assess the tumorigenicity of GC cells in vivo.RESULTS:MiR-107 was up-regulated, while FAT4 was down-regulated in GC tissues and cells (P < 0.05); FAT4 was targeted and negatively regulated by miR-107. Down-regulating miR-107 or up-regulating FAT4 inhibited the GC cells proliferation, migration, invasion and tumorigenicity, and could also reduce the expression of N-cadherin, vimentin, p-PI3K and p-Akt expression and up-regulate E-cadherin.CONCLUSIONS:miR-107 promotes growth and metastasis in GC via activation of PI3K-AKT signaling by targeting FAT4, which may be a target for GC treatment.
Cancer medicine 2019
OBJECTIVE:To investigate the effect of rosmarinic acid (RosA) on hepatocellular carcinoma cell in vivo and in vitro and to explore its possible mechanism of anti-hepatocarcinoma.METHODS:The hepatocellular carcinoma cell line SMMC-7721 was treated with different concentrations of RosA (0, 20, 50, 100 μmol/L) to detect cell proliferation, cell cycle, apoptosis and invasion.PI3K pathway-specific activator IGF-1 was used to explore whether the mechanism for RosA action relates to PI3K/AKT signal pathway.Nude mice inoculated with SMMC-7721 cells were treated with different doses of RosA (0, 5, 10 and 20 mg/kg) to detect the tumor formation of cancer cells in vivo.RESULTS:RosA significantly inhibited the proliferation of SMMC-7721 cells and induced G1 arrest and apoptosis in a dose-dependent manner. RosA might inhibit cell invasion by regulating epithelial-mesenchymal transition. Rescue experiments showed that IGF-1 could reverse the inhibition of PI3K/AKT/mTOR signal pathway by RosA and the effect on proliferation, apoptosis, cell cycle, invasion and EMT by IGF-1 in SMMC-7721 cells;RosA could inhibit tumor formation of SMMC-7721 cells in vivo.CONCLUSION:RosA can inhibit the proliferation and invasion of hepatocellular carcinoma cell in vitro and inhibit tumour growth in vivo and the mechanism may relate to inhibiting the activation of PI3K/AKT signal pathway.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2019
