Abstract
We investigated whether Analgecine treatment enhanced the antitumor response of radiotherapy in non-small cell lung cancer (NSCLC) cells. Lewis lung carcinoma (LLC) xenograft mice treated with Analgecine plus irradiation showed reduced tumor growth and increased survival. Tumor cell apoptosis was enhanced by Analgecine, based on TUNEL assays. It also increased plasma levels of pro-inflammatory cytokines (IL-6, IL-12, and IFN-γ) and decreased anti-inflammatory cytokines (TGFβ and IL-10), suggesting an enhanced immune response. Analgecine plus irradiation reduced cell viability and colony formation by A549 NSCLC cells. Analgecine treatments also activated apoptotic signaling with increased levels of pro-apoptotic proteins, including cytochrome c, caspase-3, cleaved caspase-3, caspase-9, p53 and Bax, and decreased Bcl2. Analgecine enhanced G2/M phase arrest in A549 cells by decreasing cyclinB1 and CDK1. These observations demonstrate that Analgecine combined with radiotherapy enhances anti-tumor responses by inducing apoptosis and cell cycle arrest. Moreover, they suggest possible future clinical application of Analgecine for the treatment of NSCLC.
Highlights
Lung cancer is a leading cause of cancer deaths worldwide and non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancers [1]
We investigated the therapeutic effects of Analgecine alone or in combination with radiotherapy using the xenograft Lewis lung carcinoma (LLC) mice model
The Kaplan Meier survival analysis demonstrated that treatment with Analgecine alone or in combination with ionizing radiations (IR) prolonged the survival of mice (Figure 1B)
Summary
Lung cancer is a leading cause of cancer deaths worldwide and non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancers [1]. The ionizing radiations (IR) enhance antitumor response by inducing apoptosis in tumor cells [5]. Radiotherapy with high-dose ionizing radiation is associated with adverse effects including neural damage, chronic pain and radioresistance [3, 6]. IR affects inflammatory factors in the tumor microenvironment, resulting in chronic pain that impacts the quality of life for most patients [7, 8]. There is urgent need for strategies to overcome the adverse effects due to radiotherapy. Adjuvant therapies have been used to improve the IR response and reduce IR injury to reduce chronic pain [9,10,11]. Adverse side effects of the adjuvant therapy have restricted their use in the clinic. Newer therapeutics that enhances adjuvant treatment safety and efficacy are urgently needed
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