Background: Ovarian cancer (OC) is the seventh most common cancer in women and remains a leading cause of gynecologic cancer mortality worldwide and the prevalence continues to rise especially in countries where women consume a ‘Western-style’ diet. Epidemiologic, preclinical and clinical studies suggest a potential role for dietary intake on the incidence and progression of various cancers of the body. As such, there is interest in understanding the role of diet on the development and progression of OC.
Objective: In this study we investigated the effects of different dietary protein content or quality on OC development, also the potential role of diet modulation as adjunct to anticancer drugs has been investigated.
Method: To test our hypothesis we assessed the inhibitory effect of protein diet restriction alone or in combination with anticancer drug on ovarian cancer growth, serum IGF- 1 concentrations, and mTOR activity, by injecting HM-1 cell line subcutaneously (SC) and intraperitoneally (IP) into immune competent mice.
Results: Our results showed a 16.3% (p< 0.0078, 95% CI= 21.81 to 58.72), 18.8% (p< 0.0001, 95% CI= 21.81 to 58.72) inhibition of tumor growth of SC and IP ovarian cancer model respectively with 20% plant protein diet when compared to 20% animal protein diet. Also we observed 7.4% (p< 0.01, 95% CI= 7.69 to 24.19), 5.2% ((p< 0.01, 95% CI=5.5 to 23.16) reduction of SC tumor growth when compared 20% with 10% of animal protein diet and plant protein respectively. Inhibition of tumor growth correlated with IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining. Anticancer drug significantly decrease tumor size, mice body weight and affect general condition as well,
The overall response rate to chemotherapy was 75%; more reduction in plant protein fed group when compared with animal protein fed group (p< 0.007), there was significant differences in mice bodyweight for plant protein fed compared to animal protein fed groups (p< 0.001), and the overall survival of the plant protein fed group (median 49 days) was longer than that of the animal protein fed group (median 36 days) this was statistically significant (log rank P =0.0007).
Conclusions: Our findings suggest that a reduction in dietary protein intake is effective in inhibiting tumor growth in syngeneic ovarian cancer mice models, possibly through the inhibition of the IGF/AKT/mTOR pathway. Also, our finding suggest that high plant protein diet protect against the damaging effects of chemotherapy while simultaneously increasing the effectiveness of the chemotherapy.