Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of paclitaxel octreotide conjugate on human ovarian paclitaxel-resistant cell xenograft tumor model and the mechanism underlying reversal of paclitaxel resistance

Hui Guo¹, Jing Ma², Shifa Yuan³, Ying Wang²

¹Department of Obstetrics, The Fourth Hospital, Hebei Medical University, Shijiazhuang 050011, China; ²Department of Gynecology, The Fourth Hospital, Hebei Medical University, Shijiazhuang 050011, China; ³Department of General Surgery, Hospital of Hebei Province Crop of Chinese People's Armed Police Force, Shijiazhuang 050081, Hebei Province, China.

For correspondence:- Ying Wang Email: Y15032818018@163.com

Accepted: 2 October 2023 Published: 31 October 2023

Citation: Guo H, Ma J, Yuan S, Wang Y. Effect of paclitaxel octreotide conjugate on human ovarian paclitaxel-resistant cell xenograft tumor model and the mechanism underlying reversal of paclitaxel resistance. Trop J Pharm Res 2023; 22(10):2119-2126 doi: 10.4314/tjpr.v22i10.13

© 2023 The authors.
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Abstract

Purpose: To determine the effect of paclitaxel octreotide conjugate (POC) on human ovarian paclitaxel-resistant cell xenograft tumor model and the mechanism underlying reversal of paclitaxel resistance.

Methods: Forty female BALB/c-nu/nu mice were subcutaneously inoculated with 10⁶ paclitaxel-resistant cells (a2780/taxol) per mouse during the logarithmic growth phase of ovarian cancer. They were randomly divided into four groups (control, octreotide, paclitaxel and POC). Immunohistochemical streptavidin-peroxidase (SP) method was used to determine expression of nuclear proliferation antigen (PCNA) while TUNEL method was used to assess apoptosis of human ovarian cancer metastasis. Real-time polymerase chain reaction (PCR) was used to assay mRNA expression levels of somatostatin receptor 2 (SSTR2), multidrug-resistant gene (MDR1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and acetylated tubulin (α-tubulin and β-III-tubulin), while the corresponding protein expressions were assayed using western blotting.

Results: Immunohistochemical SP showed significantly lower PCNA levels in octreotide, paclitaxel and POC groups than in control mice, but that of POC mice was significantly reduced, relative to those of octreotide and paclitaxel groups (p < 0.05). There were significantly higher expression levels of SSTR2 mRNA and protein in octreotide, paclitaxel and POC groups than in control mice, but they were significantly higher in POC group than in octreotide and paclitaxel groups (p < 0.05). The mRNA and protein expressions of other factors in POC mice were significantly lower than those in both octreotide and paclitaxel groups (p < 0.05).

Conclusion: Paclitaxel-octreotide conjugate effectively inhibits the growth of a2780/taxol xenografts in nude mice, induces tumor cell apoptosis, and suppresses tumor cell growth via mechanism involving enhancement of SSTR2 expression, and decreases in levels of acetylated tubulin, matrix metalloproteinase-9, and vascular endothelial growth factor.

Keywords: Paclitaxel octreotide conjugate, Ovarian cancer, Xenograft tumor model, Nude mice, Reversal, Paclitaxel resistant cells, Mechanism