Cisplatin (cis-dichlorodiamine platinum, CDDP) is a potent antitumor agent. However, its clinical application is limited by its side effects and the development of drug resistance. Tannic acid (TA) has previously been reported to suppress tumor growth in different types of cancer. The present study evaluated the anticancer efficacy of TA in combination with CDDP on the liver cancer cell line HepG2, and investigated the associated underlying molecular mechanisms. The results revealed that treatment with TA or CDDP alone inhibited HepG2 cell growth, with a half maximal inhibitory concentration of 360 µM and 1.8 µg/ml, respectively. The combination of TA and CDDP induced mitochondria-mediated apoptosis in HepG2 cells and significantly enhanced the growth inhibitory effect compared with TA or CDDP treatment alone. The results obtained from the present study suggest that the combination of TA and CDDP may exert synergistic anticancer effects and may be a novel adjuvant treatment for liver cancer.
Gene fusion is a molecular event occurring in cellular proliferation and differentiation, and the occurrence of irregular fusion gene results in various malignant diseases. So, sensing fusion gene with high performance is an important task for integrating individual disease information. Here, we proposed a nonenzymatic and high-throughput fluorescent assay system for the detection of fusion gene by employing DNA nanotweezers with hydrolytic activity. This tweezer was assembled by three single-stranded DNAs and engineered with sensing elements and reporting subunits. In the absence of the fusion gene, the engineered tweezer remained opened and inactive which led to no signal output. However, the addition of fusion genes would cause structure alterations of the tweezer from open to close and further DNAzyme activation with the assembly of two reporting subunits. Then, the activated DNAzyme catalyzed fluorescence substrates for signal conversion. Taking BCR/ABL fusion gene as an example, the tweezer-based assay system showed not only excellent distinguishing capability towards different input targets but also high sensitivity with a detection limit of 5.29 pM. In addition to good detection performance, this system was simple and enzyme-free, offering a powerful nanometer tool as a smart nanodevice for sensing fusion detection.
Background: Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor
growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis.
Methods: Cell lines were treated with CDDP, TA, and CDDP+TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the expression of key factors in the ER stress apoptotic pathway was detected using qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated.
Results: The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP+TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher.
Conclusions: The combination of TA and CDDP may produce synergistic antitumoral effects, mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.
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