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.