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.
Highlights
Lung cancer is the most prevalent cancer globally [1], in which non-small cell lung cancer (NSCLC)accounts for 85% of total lung cancer [2]
NSCLC has a propensity to metastasize to distal organs, and no effective therapies are able to contain the disease at this stage [5]
Our results suggest that total nutrition formula (TNuF) is a potent radiosensitizer with a marked anti-tumor/cachexia/metastasis effect on NSCLC-bearing mice
Summary
Accounts for 85% of total lung cancer [2]. Because of no effective early detection, two thirds of total lung cancers diagnosed with NSCLC at stages IIIB or IV. NSCLC has a propensity to metastasize to distal organs, and no effective therapies are able to contain the disease at this stage [5]. Radiotherapy is an alternative therapy for inoperable patients with stage I NSCLC, or for NSCLC patients with locally advanced unresectable lesions, or poor prognostic factors [6,7,8]. The treatment is further compromised because of poor radiosensitivity of cancer cells [11,12,13,14,15]. What makes the matter worse is that NSCLC has long been regarded as a radioresistant malignancy [6,17], making radiotherapy a suboptimal treatment [18]
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