Differential molecular mechanism of docetaxel–octreotide combined treatment according to the docetaxel-resistance status in PC3 prostate cancer cells

Abstract

To examine the effect and the molecular mechanisms of the combined treatment of the somatostatin (SST) analogue octreotide with docetaxel: analysis of proliferation, apoptosis and migration in the human prostate cancer cell line PC3, either sensitive (PC3wt) or made resistant to docetaxel (PC3R). We examined the effect of the two drugs individually or in combination on cell proliferation and migration by analysis of apoptosis and cell cycle proteins. The role of octreotide in modulating P-glycoprotein function was examined together with the modulation of SST receptors type 2 and 5 (SSTR2 and SSTR5). We observed an enhanced effect of docetaxel and octreotide given in combination or in sequence compared with either agent alone; this result was particularly evident when docetaxel was given before octreotide in PC3wt and when the two drugs were given together in PC3R cells. In contrast to lanreotide, our data indicate that octreotide does not act as a P-glycoprotein inhibitor in PC3R cells. A role of docetaxel and combined treatment in regulating SSTR2, SSTR5, proliferation and apoptosis gene expression is suggested as the possible mechanism for the enhanced effect observed. In addition, an evaluation of the effect of the combined treatment on cellular migration was examined, showing a moderate loss of invasive properties in PC3R cells. The present results confirm that SST analogues may be combined with docetaxel to increase the antitumour effect in patients with advanced prostate carcinoma.

Synergistic Antitumor Activities of Docetaxel and Octreotide Associated with Apoptotic-Upregulation in Castration-Resistant Prostate Cancer

“…These results suggest that OCT synergistically potentiates the efficacy of microtubule-targeting agents in PCa cells in vitro. These consistent with the recent study by Lattanzio et al docetaxel combined with octreotide synergistically enhanced the effect of combined treatment in a particularly docetaxel-resistant PC-3 cell line [24]. However, we found either of the two drugs alone stimulates proliferation of DU145 cells in a lower concentration of DTX<1 nM or OCT<10 nM respectively, which was not observed in their combined group.…”

Neuroendocrine differentiation in castration-resistant prostate cancer: A case report

“…In conclusion, the results presented above, also supported by other studies on the molecular mechanism of the docetaxel-octreotide combination (15), suggest that, in carefully selected cases, somatostatin analogues such as octreotide may be added to standard chemotherapy with docetaxel. The present study also recommends that the selection of the cases includes histological confirmation of the neuroendocrine nature of CRPC, as well as somatostatin receptor scintigraphy.…”

Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin

“…SSTR5 knockout mice develop islet neoplasia associated with enlarged islets (Wang et al, 2004, 2005a,b). Due to its differential expression, SSTR5 is involved in tumorigenesis and drug responsiveness of a variety of human cancers including pancreatic cancer (Reubi et al, 1988; Li et al, 2011; Zhou et al, 2011a; Kaemmerer et al, 2013), pancreatic endocrine tumors (PETs) (Zhou et al, 2011b, 2012; Kaemmerer et al, 2013), pulmonary neuroendocrine tumors (Tsuta et al, 2012), gastroenteropancreatic neuroendocrine tumors (Kim et al, 2011a; Sclafani et al, 2011), small cell lung cancer (Oddstig et al, 2011), gallbladder cancer (Guo et al, 2013), colon cancer (Wang et al, 2013), endocrine pituitary tumors (Nishioka et al, 2011; Mayr et al, 2013; Chinezu et al, 2014), thyroid cancer (Ocak et al, 2013), corticotroph adenomas (Fleseriu and Petersenn, 2013), prostate cancer (Gu et al, 2010; Mazzucchelli et al, 2011; Lattanzio et al, 2013), and breast cancer (Gu et al, 2010). SSTR5 is also involved in the regulation of angiogenesis (Zatelli et al, 2001) and apoptosis (Qiu et al, 2006; Wang et al, 2013).…”