Preoperative hyperfractionated accelerated irradiation-induced apoptosis in non-small cell lung cancer

Abstract

To study the apoptosis inducing effect of preoperative hyperfractionated accelerated radiation therapy (HART) and expression of Bcl-2, Bax proteins in non-small cell lung cancer. From October 1999 to March 2001, 81 patients with non-small cell lung cancer were prospectively divided into preoperative HART group (20 patients) and surgical group (61 patients). The patients in preoperative HART group were given preoperative irradiation with 2.5 Gy/fraction, twice a day to a total dose of 25 Gy/10 fractions/5-7 days using anterior-posterior opposing parallel fields, then operation would be performed within 2 weeks. The patients in surgical group only received surgical treatment. Apoptotic index (AI), cell cycle distribution and expression of Bcl-2, Bax proteins were quantitatively analyzed by indirect-immunofluorescene and flow cytometry. AI was 4.6%±2.3% in surgical group and 12.8%±4.3% in preoperative HART group, respectively ( P < 0.001). There was no difference in S phase fraction (SPF) between the two groups ( P > 0.05). The fluorescence index (FI) for Bcl-2, Bax proteins and the ratio of Bcl-2/Bax were 1.33±0.21, 1.05±0.13 and 1.29±0.23 in surgical group, and 1.14±0.26, 1.19±0.16 and 0.96±0.23 in preoperative HART group respectively ( P < 0.01, P < 0.001 and P < 0.001 respectively). AI showed a positive correlation to Bax protein ( P < 0.001) and a negative correlation to the ratio of Bcl-2/Bax ( P < 0.01). Preoperative HART may induce a high-level apoptosis by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein. However, it is still necessary to further observe whether it can improve the long-term survival of patients with NSCLC.