Synthetic paclitaxel-octreotide conjugate reverses the resistance of paclitaxel in A2780/Taxol ovarian cancer cell line

Abstract

The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity. In the present study, we prepared the POC and investigated its effects and mechanism for the reversal of drug resistance in paclitaxel-resistant ovarian cancer cell line. We demonstrated that treatment with POC led to more cell apoptosis than either paclitaxel or octreotide (OCT) alone. Moreover, the expression of multidrug resistance 1 (MDR1) and vascular endothelial growth factor (VEGF) mRNA, and protein decreased in a dose-dependent manner while the expression of SSTR remained stable following treatment with POC. Although the exact action, in vivo effects and pharmacologic kinetics of POC remain to be investigated, we have demonstrated the feasibility for the synthesis of POC, and more significantly, provided a potential approach to overcome the resistance of ovarian cancer against taxol. The findings also shed some new light on the mechanisms underlying the development of resistance to taxol by ovarian cancer cells.

Treatment with β-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway

“…Previous reports have found that STAT3 and NF-kB signal pathways involved in growth and invasion of ovarian cancer cells (30)(31)(32)(33). Evidence has shown that paclitaxel can be regarded as an efficient therapy for human ovarian cancer and the therapy of paclitaxel combined with other drugs provides a potential approach to overcome the resistance of ovarian cancer (34)(35)(36). Pashaei-Asl et al (17) reported that combination of the chemotherapy drugs silibinin and paclitaxel can be more efficient in treatment of ovarian cancer cells.…”

Octreotide-Paclitaxel Conjugate Reverses Paclitaxel Resistance by p38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in A2780/Taxol Human Ovarian Cancer Cells

“…We preliminary synthesized octreotide-paclitaxel conjugate (POC, patent No. : ZL 2013 1 2013 X), and experimental studies of the resistance to A2780/Taxol cells and tumor-burdened nude mice confirmed that the octreotide-paclitaxel conjugate has a highly property of targeting [ 11 ]. Tumor-burdened nude mice experiments in vivo observed that octreotide-paclitaxel conjugate effectively inhibited ovarian cancer resistance cell A2780/Taxol proliferation, increased the sensitivity of the A2780/Taxol cells to paclitaxel (PTX), and octreotide-paclitaxel conjugate showed low toxicity to normal organs [ 12 ].…”

Identification and imaging of miR-155 in the early screening of lung cancer by targeted delivery of octreotide-conjugated chitosan-molecular beacon nanoparticles

“…Five subtypes of somatostatin receptors SSTRs, namely SSTR1-5, and SSTR2 expression are seen in most of these tumors (Shahbaz et al., 2015; Kharmate et al., 2013). Artificially synthesized somatostatin analog (SSTA) such as octreotide (OCT) could specifically bind to SSTR2 to achieve the purpose of targeting tumor cells with SSTR2 expression (Ju et al., 2018; Shen et al., 2017).…”