Potential anti-tumor effect of a nanoliposomal antiPCSK9 vaccine in mice bearing colorectal cancer

Abstract

Introduction: Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an effective therapeutic tool for lowering low-density lipoprotein cholesterol (LDL-C). There is no available evidence on the efficacy and safety of PCSK9 inhibitors in non-cardiovascular diseases, particularly cancer. The present study aimed to evaluate the effect of PCSK9 inhibition on cancer endpoints in mice bearing colon carcinoma, using a nanoliposomal antiPCSK9 vaccine. Material and methods: The prepared nanoliposomal antiPCSK9 vaccine was subcutaneously inoculated in BALB/c mice four times with a biweekly interval. Two weeks after the last booster, the vaccinated and unvaccinated mice were subcutaneously inoculated with CT26 colon cancer cells into the right flank. After the tumor mass became palpable, the mice were randomly divided into three groups: (1) PBS (untreated control), (2) vaccine group, and (3) pegylated liposomal doxorubicin (PLD; positive control) group. Body weight, tumor size and survival of mice were monitored for 50 days. Results: The nanoliposomal antiPCSK9 vaccine could efficiently provoke specific antibodies against PCSK9 in BALB/c mice and thereby reduced the plasma level and function of PCSK9. Tumor volume was 77% and 87.7% lower (p < 0.0001) in the vaccinated mice when compared with Doxil (liposomal doxorubicin) and control mice, respectively. Tumor size analysis showed that time to reach the endpoint of the vaccine group (47 ±11 days) was slightly but not significantly higher than PLD (46 ±2.6 days) and the control (43 ±12 days) groups. The tumor growth rates in the vaccine and PLD groups were reduced by 9.3% and 7.3, respectively, when compared with the control group. The vaccinated mice survived slightly but not significantly longer than PLD and the control mice. The median survival of the vaccine, PLD and control groups were 51, 45, and 41 days, respectively. The vaccinated mice’s life was prolonged by 24.4% as compared with the control mice, while it was increased by 9.8% in the PLD group. Conclusions: Our results revealed that PCSK9 inhibition not only exerted no harmful effects but also could moderately inhibit tumor growth, and improve lifespan and survival in mice bearing colon cancer.