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

Nutrients. 2019 Aug 18;11(8):1944. doi: 10.3390/nu11081944.

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.

Keywords: cachexia; non-small-cell lung cancer (NSCLC); radiosensitization; radiotherapy; total nutrition formula (TNuF).

MeSH terms

  • Animals
  • Apoptosis
  • Cachexia
  • Carcinoma, Lewis Lung
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Dietary Supplements*
  • ErbB Receptors / metabolism
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic
  • Nutrients / therapeutic use*
  • Nutrition Therapy*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Signal Transduction
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / metabolism
  • Weight Gain
  • Xenograft Model Antitumor Assays

Substances

  • Radiation-Sensitizing Agents
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • EGFR protein, mouse
  • ErbB Receptors