Enhancement of Recombinant Human Endostatin on the Radiosensitivity of Human Pulmonary Adenocarcinoma A549 Cells and Its Mechanism

Abstract

We observed the effects of endostar on the radiosensitivity of pulmonary adenocarcinoma A549 cells and found that endostar inhibited A549 cell growth under normoxia and hypoxia in time and dose-dependent manners; the D0 and Dq values in control and endostar groups were (1.36 and 1.30) versus (1.019 and 1.015) under normoxia and (1.693 and 1.39) versus (2.453 and 1.026) under hypoxia, respectively; SER was 1.04 under normoxia and 1.22 under hypoxia in endostar group; under normoxia, the apoptosis rates in control, radiotherapy, endostar and combination groups were 15.9 ± 0.57%, 42.7 ± 0.37%, 19.9 ± 0.48%, and 41.5 ± 0.38%, respectively, with no significant difference between combination and radiotherapy groups; there was significant difference in G2/M phase cells between combination and radiotherapy groups (P = 0.028); under hypoxia, the apoptosis rates in the four groups were 16.7 ± 0.67%, 30.1 ± 0.95%, 26.7 ± 0.62%, and 36.3 ± 0.71%, respectively, with significant difference between combination and radiotherapy groups; G2/M phase cells were higher in combination group than radiotherapy group (P = 0.000); G2/M phase cells were higher in hypoxic combination group than in normoxic combination group (P = 0.003). Based on these results, we conclude that under hypoxia, endostar can enhance the radiosensitivity of A549 cells through G2/M arrest.

Efficacy and safety of recombinant human endostatin combined with radiotherapy or chemoradiotherapy in patients with locally advanced non-small cell lung cancer: a pooled analysis

“…Of note, the duration and intervals of endostatin and radiotherapy combinations differed in clinical trials and may affect the outcomes (as shown in Table 1). Results from preclinical studies showed that endostatin treatment could transiently normalize the tumor vasculature by reducing microvessel density and increasing pericytic coverage of the vessel endothelium, thereby providing a time window (about 1 week) to enhance the sensitivity to RT; thus, RT delivery in this period resulted in maximal anti-tumor outcomes [15,49]. CT perfusion imaging and hypoxia imaging suggested that the "time window" was within about 1 week after administration, during which endostatin improved blood perfusion and decreased hypoxia of lung cancer [14].…”

Different administration routes of recombinant human endostatin combined with concurrent chemoradiotherapy might lead to different efficacy and safety profile in unresectable stage III non‐small cell lung cancer: Updated follow‐up results from two phase II trials

“…1,2,15,29,30 In our study, the patients received 3D-CRT in the IV arm and IMRT in the CIV arm. Modern techniques such as IMRT have improved target coverage using optimized modulated fields (typically [6][7][8][9][10][11][12]. IMRT might bring substantial benefits in prognosis compared to 3D-CRT.…”

“…In 2009, we initiated a prospective phase II clinical study applying an intravenous injection (IV) of Endostar with CCRT for patients with locally advanced NSCLC which showed promising survival and local control rates . Based on preclinical data the inhibition effect of Endostar on tumor cells is time‐dependent . Continuous intravenous pumping (CIV) is considered a better administration route to maintain a steady blood concentration and might improve efficacy.…”

“…7 Based on preclinical data 8,9 the inhibition effect of Endostar on tumor cells is time-dependent. 10 Continuous intravenous pumping (CIV) is considered a better administration route to maintain a steady blood concentration and might improve efficacy. In addition, since continuous intravenous pumping is more convenient for patients, it can also enhance treatment compliance.…”

“…In 2012, we initiated another phase II study (named HELPER) of Endostar CIV combined with CCRT for patients with locally advanced NSCLC and achieved preferable overall survival (OS), promising two-year progressionfree survival (PFS) and favorable distant metastasis-free survival (DMFS) with acceptable toxicities. 10 However, whether Endostar CIV is superior to IV in addition to CCRT for patient with unresectable NSCLC remains unclear because until now direct comparisons of the two administration routes have mostly been performed in advanced NSCLC or ovarian cancer patients treated with chemotherapy and the study design of the only study carried out in patients treated with Endostar combined with chemoradiotherapy was poor as it included all kinds of advanced malignant tumors and the chemoradiotherapy was not fixed. 12 Therefore, we prolonged the follow-up of our two studies as mentioned above and attempted to provide evidence for different administration routes of Endostar combined with CCRT in patients with unresectable stage III NSCLC.…”