Inhibition of PI3K increases oxaliplatin sensitivity in cholangiocarcinoma cells

Abstract

Background: Resistance of cholangiocarcinoma to chemotherapy is a major problem in cancer treatment. The mechanism of resistance is believed to involve phosphoinositide-3-kinase (PI3K)/ Akt activation. Although the platinum-containing compound oxaliplatin has been extensively used in the treatment of several solid tumors, recent data regarding its use to treat cholangiocarcinoma are ambiguous. Oxaliplatin resistance in this disease could potentially involve PI3K pathways. We, therefore, examined the effects of PI3K pathways in cholangiocarcinoma cells in modulating oxaliplatin resistance.

Induction of MKP-1 prevents the cytotoxic effects of PI3K inhibition in hilar cholangiocarcinoma cells

“…Western blot analyses were performed as previously described (Leelawat et al 2009). The blots were Wrst probed with antibodies against phospho-Akt, phospho-p38 MAPK and MKP-1 and then reprobed with antibodies against total Akt, p38 MAPK and -tubulin.…”

“…Previously, we also demonstrated that PI3K is constitutively activated in KKU-100 cells. However, treating the KKU-100 cells with LY294002 (a speciWc inhibitor of PI3K) does not inhibit the proliferation of these cells (Leelawat et al 2009). Therefore, in this study we aimed to elucidate the mechanism by which KKU-100 cells resist PI3K inhibition.…”

The Src/PI3K/Akt signal pathway may play a key role in decreased drug efficacy in obesity‐associated cancer

“…It could have synergistic effect with chemotherapy drugs. It has been demonstrated in cholangiocarcinoma cells, the inhibition of PI3K increased oxaliplatin cytotoxicity [Leelawat et al, 2009]. In colon cancer, inhibition of PI3K has also been shown to increase the cytotoxicity of low dose of BBR3610 [Mitchell et al, 2007].…”

Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells

“…Furthermore, sorafenib-released media was used to test whether sorafenib maintained its biological activity during the stent-coating process and drug-release experiment. At 1,5,10,15,20, and 30 days of the drug-release experiment, the collected media were used to test anticancer activity.…”

“…1 reported with combinations of anticancer drugs. [4][5][6][7][8][9] Among them, clinical trials with a combination of gemcitabine plus cisplatin were reported to have significant survival advantage compared to gemcitabine alone.…”