Antimetastatic effect of fluvastatin on breast and hepatocellular carcinoma cells in relation to SGK1 and NDRG1 genes

Abstract

Metastasis occurs due to migration of the cells from primary tumor toward other tissues by gaining invasive properties. Since metastatic invasion shows a strong resistance against conventional cancer treatments, the studies on this issue have been focused. Within this context, inhibition of migration and determination of the relationships at the gene level will contribute to treatment of metastatic cancer cases. We have aimed to demonstrate the impact of TGF-β1 and fluvastatin on human breast cancer (MCF-7) and human hepatocellular carcinoma (Hep3B) cell cultures via Real-Time Cell Analyzer (RTCA) and to test the expression levels of some genes (NDRG1, SGK1, TWIST1, AMPKA2) and to compare their gene expression levels according to RTCA results. Both of cell series were applied TGF-β1 and combinations of TGF-β1/fluvastatin. Primer and probes were synthesized using Universal Probe Library (UPL, Roche) software, and expression levels of genes were tested via qPCR using the device LightCycler 480 II (Roche). Consequently, fluvastatin dose-dependently inhibited migration induced by TGF-β1 in both groups. This inhibition was accompanied by low level of SGK1 messenger RNA (mRNA) and high levels of NDRG1 and AMPKA2 mRNA. Thus, we conclude that fluvastatin plays an important role in reducing resistance to chemotherapeutics and preventing metastasis.

Serum and Glucocorticoid Inducible Kinase 1-Sensitive Survival, Proliferation and Migration of Rhabdomyosarcoma Cells

“…Moreover, the sensitivity of RMS cell lines to the cytotoxic drug doxorubicin was enhanced, which is in complete accordance with reports that show SGK1 supporting cell proliferation, stimulating their migration and counteracting apoptosis in diverse tumor cell types [16, 29], including colorectal carcinoma [11-13, 16, 45], hepatocellular carcinoma [17, 18], breast cancer [18-20], prostate cancer [21, 22], glioblastoma [23-25], non-small cell lung cancer [26], meningiomas [27] and medulloblastoma [28]. …”

“…Mechanisms conferring tumor cell survival and therapy resistance include the serum & glucocorticoid inducible kinase SGK1, initially identified in mammary tumor cells [8-14], yet then found as being ubiquitously expressed with strong emphasis in skeletal muscle [15] and highly upregulated in different tumors such as colonic cancer [16], hepatocellular carcinoma [17, 18], breast cancer [18-20], prostate cancer [21, 22], glioblastoma [23-25], non-small cell lung cancer [26], meningiomas [27], and medulloblastoma [28]. Several studies demonstrate a pivotal role for SGK1 in cell survival, cell proliferation and migration of tumor cells [16, 29].…”

Susceptibility of lactic acid bacteria, bifidobacteria and other bacteria of intestinal origin to chemotherapeutic agents

“…Decreases in the CI are due to any effect causing cytotoxicity, structural damages, apoptosis, and/or inducing morphological modifications (in either shape or size) to the cells (Xi et al, 2008). The suitability and accuracy of measuring the CI of cell cultures by the RTCA technology for evaluating the cytotoxic degree of antitumorals has been recently reported (Salis et al, 2015;Benay et al, 2015). In this sense, the cytotoxic effect of afatinib on a human-derived cell line (HT29) through the use of an RTCA approach is being reported for the first time.…”

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

“…It is a PI3k-I/mTORC2 down-stream kinase induced by glucocorticoid, TGF-b, IL-2, and IL-6. Its activation has been shown to inhibit chemotherapy induced apoptosis in ovarian cancer and to promote cell migration, invasion, and metastasis in lung, hepatocellular, and colon cancers [71][72][73][74] the differential modulation of mRNAs and miRNAs by RV and IL-6 described above.…”