Endostar enhances the antitumor effects of radiation by affecting energy metabolism and alleviating the tumor microenvironment in a Lewis lung carcinoma mouse model

Abstract

Abstract. Lung cancer is a leading cause of morbidity and mortality. Previous studies have identified that an improvement in treatment efficacy was achieved using Endostar; however, the role of Endostar in lung cancer remains poorly understood. The present study investigated whether the enhanced antitumor effects of Endostar in combination with radiation involved changes in the metabolism and microenvironment in non-small cell lung cancer. A Lewis lung carcinoma mouse model was used, including the control, Endostar (ES), radiotherapy (RT) and Endostar plus radiotherapy (ES + RT) groups. The tumor inhibition rates and growth were described based on changes in tumor volume. In addition, ultraviolet enzymatic analysis was performed to determine the lactate level and reverse transcription-polymerase chain reaction was used to measure the mRNA expression of lactate dehydrogenase (LDH). A Meph-3 pH meter was used to detect the ranges of tumor interstitial tissue pH, and immunohistochemical analysis was adopted to examine hypoxia within the tumor microenvironment. The tumor inhibition rate of the ES + RT group was significantly higher compared with the other three groups (P<0.05). Following treatment, the lactate levels decreased in all three treatment groups compared with the control, particularly in the ES + RT group (P<0.05). Reduced LDH expression and hypoxic fraction in the tumor microenvironment were also observed in the ES + RT group (P<0.05). Furthermore, changes from acidic to alkaline pH in the tumor microenvironment were detected in the ES + RT group. The present study suggested that Endostar is involved in the regulation of metabolism and tumor microenvironment hypoxia, which may be responsible for the enhanced antitumor effect of Endostar in combination with radiotherapy.

Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer

“…Tumor volumes were calculated according to the formula V = a × b 2 × 0.5, where a was the longest diameter and b was the maximum transverse diameter. The tumor volumes were measured up to 17 days with a vernier caliper, and then the mice were sacrificed, and tumors from each group were surgically excised, rinsed with PBS, wiped, weighed, and photographed (Meng et al., 2013 ; Zheng et al., 2015 ; Zhu et al., 2015 ; Tang et al., 2019 ).…”

Five-year survival rate analysis: the combination of fortnightly-administration of endostar and concurrent chemoradiotherapy versus concurrent chemoradiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer

“…Besides, previous study revealed that Endostar was involved in the regulation of both metabolism and tumor microenvironment hypoxia, which may be responsible for enhanced antitumor effects of Endostar combined with radiotherapy (43). For inoperable locally advanced NSCLC, further exploration and research into whether the addition of Endostar on the basis of the new standard of CCRT plus consolidation immunotherapy can further improve the therapeutic effects and also play a role in radiological protection is warranted.…”

Combining novel agents with radiotherapy for gynecologic malignancies: beyond the era of cisplatin

“…Another hypoxia modifier, Endostar (recombinant human endostatin), is a novel artificially synthesized anti-angiogenic agent that has been approved for clinical use. Endostar has been found to enhance the anti-tumor effects of radiation therapy by altering the tumor’s energy metabolism and micro-environment through hypoxia modification, as demonstrated in murine models 89. The addition of Endostar to chemo-radiation therapy is being evaluated in both a phase II study of patients with postoperative high-risk early-stage cervical cancer (NCT03622827, Table 3) and a multi-institutional phase III study of women with cervical cancer (FIGO (2009) stage Ib, IIa2, IIb–IVa) (NCT03086681, Table 3).…”