Antitumor, Inhibition of Metastasis and Radiosensitizing Effects of Total Nutrition Formula on Lewis Tumor-Bearing Mice

Abstract

Non-small-cell lung cancer (NSCLC) causes high mortality. Radiotherapy is an induction regimen generally applied to patients with NSCLC. In view of therapeutic efficacy, the outcome is not appealing in addition to bringing about unwanted side effects. Total nutrition is a new trend in cancer therapy, which benefits cancer patients under radiotherapy. Male C57BL/6JNarl mice were experimentally divided into five groups: one control group, one T group (borne with Lewis lung carcinoma but no treatment), and three Lewis lung carcinoma-bearing groups administrated with a total nutrition formula (T + TNuF group), a local radiotherapy plus daily 3 Gy in three fractions (T + R group), or a combination TNuF and radiotherapy (T + R + TNuF group). These mice were assessed for their mean tumor volumes, cachectic symptoms and tumor metastasis. TNuF administration significantly suppressed tumor growth and activated apoptotic cell death in NSCLC-bearing mice under radiation. The body-weight gain was increased, while the radiation-induced cachexia was alleviated. Analysis of mechanisms suggests that TNuF downregulates EGFR and VEGF signaling pathways, inhibiting angiogenesis and metastasis. In light of radiation-induced tumor cell death, mitigation of radiation-induced cachexia and inhibition of tumor cell distant metastasis, the combination of TNuF and radiotherapy synergistically downregulates EGFR and VEGF signaling in NSCLC-bearing mice.

Nutritional Interventions in Cancer Cachexia: Evidence and Perspectives From Experimental Models

“…However, attenuation of muscle tissue loss was only observed for the suprahyoid muscles in the neck but not for gastrocnemius or soleus muscles in the lower leg ( 141 ). More recently, the effect of total nutrition formula on LLC-bearing mice was investigated ( 142 ). Total nutritional formula is an energy- and protein-dense oral nutritional supplement fortified with micronutrients such as vitamin D, vitamin A, coenzyme Q10 and selenium.…”

“…Daily oral supplementation with total nutritional formula significantly suppressed tumor growth, while body weight loss and gastrocnemius muscle mass loss were significantly attenuated. Furthermore, the plasma levels of TNF-α and IL-6 were significantly decreased in LLC-bearing mice supplemented with total nutritional formula ( 142 ).…”

Positive Effects of Preventive Nutrition Supplement on Anticancer Radiotherapy in Lung Cancer Bearing Mice

“…Although we found that TNuF can downregulate tumoral expressions of caspase 3, Bcl-2, EGFR, VEGF, and HIF-α in our previous research [ 11 ], its effect on other pro-tumoral markers, such as STAT3, Ki-67, and AXL, was not evaluated. STAT3 is closely related to the cell proliferation induced by EGFR activation [ 25 ].…”

“…The hyperactivation of the angiogenic pathway in tumor cells can trigger a regeneration of tumoral vessels during fractional irradiation, resulting in the failure of RT [ 16 ]. In our previous study, the single treatment of TNuF was shown to downregulate the angiogenic pathway in LLC tumor cells [ 11 ]. Therefore, we detected the expression of hypoxia-inducible factor 1α (HIF-1α), tyrosine-protein kinase receptor UFO (AXL) mRNA, and vascular endothelial growth factor (VEGF) mRNA to observe the effect of TNuF on the angiogenic pathway in tumor cells ( Figure 4 ).…”

“…TNuF was reported to be able to stabilize body weight, serum albumin, and prealbumin levels in patients undergoing RT [ 10 ]. We previously reported that the prescription of TNuF after tumor inoculation significantly enhances the antitumor efficacy of RT, and the combination of TNuF and RT downregulates both epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGF) pathways in tumors of NSCLC-bearing mice [ 11 ]. In contrast, the influence of early nutrition supplementation on patients who have not yet been diagnosed with cancer or contracted cancer and are not yet receiving anticancer treatment is rarely studied or discussed.…”