Progressive
tumor-bearing patients deserve to benefit from more realistic approaches. Here, a study revealed the impact of modified periodic fasting and refeeding regimen on
tumor progression or regression with little or no loss of food intake and
body weight. Human A549 lung, HepG-2 liver, and SKOV-3 ovary progressive
tumor-bearing mice were established and subjected to 4 wk of periodic fasting/refeeding cycles (PFRC), including periodic 1-d fasting/6-d refeeding weekly (protocol 1) and periodic 2-d fasting/5-d refeeding weekly (P2DF/5DR, protocol 2), with ad libitum (AL)-fed hosts as controls. Afterwards, PFRC groups exhibited
tumor growth arrest with some tendency towards regression; especially, complete regression of progressive
tumors and
metastases comprised between 43.75 and 56.25% of
tumor-challenged hosts in P2DF/5DR group (P < 0.05). AL controls, in contrast, showed continuous
tumor progression and
metastasis. Finally, 100% hosts in P2DF/5DR and 62.5-68.75% in periodic 1-d fasting/6-d refeeding weekly groups survived a 4-month study period vs. only 31.25-37.5% in AL control group. Immunological assays and Luminex microarray revealed that
tumor growth remission is mainly via natural killer cell (NK) reactivity and cross-regulation of IGF-binding protein-3, IGF/IGF-receptor, and
megakaryocyte growth and development factor autocrine and paracrine loops. In vivo cellular and humoral assays indicated that
tumor-regressive induction by PFRC protocols could be partly terminated by NK cell and IGF-binding protein-3 blockade or replenishment of
IGF-I/-II and
megakaryocyte growth and development factor. These findings offer a better understanding of comprehensive modulation of periodic fasting/refeeding strategy on the balance between
tumor progression and regression.