Phosphates and tensin homologue deleted on chromosome 10 (PTEN) is a tumour suppressor gene which dephosphorilates phosphoinositol 3,4,5 triphosphates. Therefore PTEN can regulate PI3K/AKT pathway in cells. Because of promoter methylation or gene deletion, PTEN expression is commonly decreased or lost in non-small cell lung cancer (NSCLC) cell lines. Therefore, we hypothesized that PTEN could regulate the activity of superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx) and catalase. We first recreated PTENwt, G129R and G129E expressions in lung cell lines, in which endogenous PTEN expression was not detected. Then, we showed that PTEN could suppress AKT activity by its lipid phosphatase domain. We then examined the effect of recreated PTEN expressions in NSCLC cells. While PTENwt expression caused enhanced activity of SOD, GPx and catalase in transfected cells lines, neither G129R nor G129E expression effected enzyme activities. These results suggest that PTEN can up-regulate SOD, GPx and catalase activity by inhibition of PI3K/AKT pathway in NSCLC cell lines.
Conventional and newly emerging treatment procedures such as chemotherapy, catalytic therapy, photodynamic therapy, and radiotherapy have not succeeded in reversing the outcome of cancer diseases to any drastic extent, which has led researchers to investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. It has been reported that several members of the Convolvulaceae, Iridaceae, and Liliaceae families have antitumor activity against some tumor cell lines. Here we first report that Convolvulus galaticus, Crocus antalyensis, and Lilium candidum species have cytotoxic activity on human breast cancer cell line MCF-7 cells. Plant samples were collected and identified, and their cytotoxic effects on the MCF-7 cell line were examined at different concentrations of methanol extracts. We found that all three plants have cytotoxic effects on MCF-7 cells but that C. galaticus has the strongest cytotoxic effect even in the lowest extract concentration tested (0.32 μg/mL). Our results indicate that these plant extracts have cytotoxic effects on human breast carcinoma cell line MCF-7 cells and that this cytotoxic effect comes from p53-mediated stimulation of apoptosis.
We know that detection of EGFR mutations is very important for individual therapy. Nowadays FFPE samples are commonly using to detect the EGFR mutation status. But it has a few handicaps such as, tumor heterogeneity and non-repeatable, it is need to examine mutation statues of EGFR after each treatment regimen for individually treatment of NSCLC patients. Therefore, there is still need to develop non-invasive and useable over and over again approach for monitoring EGFR mutation statues and other genes for individual therapy. So, we aim to examine whether exosomes are good target for detection of EGFR mutation status or not. Pyrosequencing was used to detect, EGFR mutation in FFPE and exosome samples in some NSCLC patients. For the patients given different chemotherapy regime (n=28), PFS was evaluated before and after treatment. In patients who were EGFR positive before treatment, the median PFS for EGFR mutation-positive patients after treatment was 101.7 weeks (95% CI: 0.09-3.21), while for patients who were negative after treatment, the median PFS was 42.43 weeks (95% CI: 0.31- 10.52). Likewise, in patients who were EGFR negative before treatment and EGFR mutation negative after treatment, the PFS was median 52 weeks (95% CI: 0.17-2.84), while in patients who were positive after treatment, the median PFS was 27.57 weeks (95% CI: 0.35-5.58). We show that exosomes are good tools for monitoring EGFR mutation status and exosomes can be use as semi-invasive method for isolation of tumor DNAs for detection of mutation statues for individually treatment of NSCLC patients.