Key protein expressions in the insulin-like growth factor-1 signal pathway involved in the resistance of ovarian cancer to cisplatin / 中国肿瘤临床

ABSTRACT

Objective: This study aimed to detect the expression levels of the key proteins involved in the insulin-like growth factor signaling pathway of patients with ovarian cancer. These proteins include insulin-like growth factor-1 (IGF1), insulin-like growth factor-1 receptor (IGF1R), and protein kinase B (AKT). Methods: Ovarian cancer tissues were subjected to drug resistance tests using the ATP-TCA method. IGF1, IGF1R, AKT, and multidrug resistance protein2 (MRP2) expressions were detected in the sera of patients with ovarian cancer by conducting enzyme-linked immunosorbent assay. IGF1, IGF1R, and AKT protein expressions were detected in the surgical specimens by immunohistochemistry. Patients were instructed to monitor their cancer antigen 125 (CA125) levels monthly from the date a patient was discharged to the last day of chemotherapy (or until chemotherapy was completed). A color Doppler ultrasound, CT, or MRI scan was required if CA125 value is abnormal. The total follow-up time was one year. Results: IGF1, IGF1R, and AKT expressions were significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group (P =0.000 1). Immunohistochemical results showed that IGF1, IGF1R, and AKT expressions were significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group (P<0.05). The monthly CA125 values of 40 patients were obtained after chemotherapy. In the cisplatin-sensitive group, 18 of the 24 cases exhibited normal CA125 values for more than one year, and the remaining 6 cases maintained normal values for more than half a year. In the cisplatin-resistant group, 16 cases revealed higher than normal CA125 values for half a year after chemotherapy. Recurrent lesions were observed in their color Doppler ultrasound results or MRI scans. Conclusion: Cisplatin resistance in ovarian cancer is strongly correlated with the expressions of IGF1, IGF1R and AKT. IGF1 is a potential candidate for the targeted therapy of ovarian cancer.