Leptin contributes to the taxol chemoresistance in epithelial ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is a gynecological malignancy with high morbidity. Treating EOC remains a challenge, as the pathogenesis of this disease remains unclear and chemoresistance is a common occurrence. A number of previous studies have revealed that obesity is closely associated with cancer and leptin, as a link between cancer and obesity, has become a focus of research in recent years. In the present study, survival database analysis demonstrated that leptin expression was associated with poor prognoses in patients treated with platinum and paclitaxel/docetaxel. A cell activity assay demonstrated that leptin reduced the chemosensitivity of ovarian cancer cells to paclitaxel/docetaxel. Furthermore, flow cytometry results revealed that treatment with exogenous leptin reduced the proportion of ovarian cancer cells in G2/M phase, which was significantly elevated following paclitaxel/docetaxel chemotherapy. It was also verified that transcription factor CCAAT/Enhancer Binding Protein α can bind to the upstream promoter region of leptin and activate its transcription in ovarian cancer cells. Together, these results suggest that leptin serves an important role in chemoresistance and may serve as a novel therapeutic target for ovarian cancer in patients treated with platinum and paclitaxel chemotherapy.

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

“…The influence of leptin on chemoresistance in epithelial ovarian cancer has been studied. Treatment with exogenous leptin decreased paclitaxel/docetaxel-induced G2/M phase cell cycle arrest in ovarian cancer cells [ 36 ]. However, experimental results from another research group showed that serum levels of leptin were not correlated with the response to paclitaxel/carboplatin therapy in ovarian cancer patients [ 37 ].…”

“…The demonstrations of main biological effects (Table 2) and signaling axes (Figure 4) induced by leptin/leptin receptor in different cancer types were shown. Ovarian Cancer ↑: [41] ↑: [38][39][40]42] ↑: (paclitaxel/docetaxel) [36] Brain Tumor ↑: [45,46] ↑: [47,48] ↑: [45] ↑: (temozolomide) [49] Breast Cancer ↑: [54,58] ↑: [53,55] Liver Cancer ↑: [60,63] ↑: [60,63] ↓: [63] ↓: [65] (rat)…”

Obesity and Energy Substrate Transporters in Ovarian Cancer—Review

“…Hence, the incubation of leptin with OC cells ameliorates the influence of paclitaxel/Taxol on cancer cell microtubules. It is worth mentioning that high levels of leptin hypothetically may have linkage with resistance to chemotherapy, but these data are unclear and need further research [ 111 ].…”

Adipocytes: active facilitators in epithelial ovarian cancer progression?

“…The main mechanism of adipocyte-induced therapy resistance is to modulate the pro-survival pathways and survival genes. It was reported adipocyte-secreted leptin contributed to the taxol chemoresistance in EOC through the activation of EMT in ovarian cancer cells [ 124 ]. Leptin could also activate AKT and ERK survival pathways in EOC cells, which are known to play crucial roles in EOC drug resistance [ 125 ].…”