[The in vitro and in vivo effects of adenovirus-mediated inhibitor of growth 4 and interleukin-24 co-expression on the radiosensitivity of human lung adenocarcinoma].

OBJECTIVE

To study the radiosensitivity of the recombinant adenoviral vector (called Ad-ING4-IL-24) carrying and co-expressing inhibitor of growth 4 (ING4) and interleukin-24 (IL-24) to human lung adenocarcinoma and the underlying mechanisms.

METHODS

The expression levels of ING4 and IL-24 were detected by Western blot. The growth-suppressing and apoptosis-inducing effect of Ad-ING4-IL-24 combined with radiotherapy on SPC-A-1 lung carcinoma cells were assessed by MTT assay and FCM respectively. The 25 nude mice were randomly divided into 5 groups of 5 mice ecah: PBS group, Ad group, Ad-ING4-IL-24 group, radiotherapy group and joint group (Ad-ING4-IL-24 combined radiotherapy). Mice in all groups except radiotherapy group were intratumorally injected every other day for 6 cycles. The short and long axes of the tumor were measured dynamically, tumor volume was calculated as: V = L × W(2/2), changes in tumor volume were graphed. The human lung carcinoma model was established with SPC-A-1 cells in nude mice. The ratios of tumor-suppression and q were calculated. The expression of Caspase-3, Bcl-2, Bax, VEGF in tumor samples were detected by immunohistochemistry.

RESULTS

The expressions of ING4 and IL-24 were successfully expressed in SPC-A-1 cells. MTT assay and FCM showed that the levels of cell-growth inhibition and apoptosis induction in Ad-ING4-IL-24 combined with radiotherapy group [(86.2 ± 0.8)%, (60.9 ± 1.0)%] were higher than in Ad-ING4-IL-24 group [(49.8 ± 0.3)%, (26.3 ± 1.3)%] and in radiotherapy group [(44.4 ± 2.2)%, (33.3 ± 0.8)%] (ratio of cell-growth inhibition, F = 550.88, P < 0.01; ratio of induced apoptosis F = 614.08, P < 0.01). Ad-ING4-IL-24 combined with radiotherapy showed an enhanced radiosensitivity effect on human lung adenocarcinoma (q = 1.20). In Ad-ING4-IL-24 group, radiotherapy group and Ad-ING4-IL-24 combined with radiotherapy group, the weight inhibition ratio was 49.5% (5 nude mice), 35.4% (5 nude mice), 79.8% (5 nude mice) respectively. Ad-ING4-IL-24 combined with radiotherapy had a synergetic and enhanced radiosensitivity effect on inhibiting the growth of transplanted tumor (q = 1.18). According to immunohistochemistry, Ad-ING4-IL-24 was shown to up-regulate the expression of Bax and Caspase-3 but down-regulate the expression of Bcl-2 and VEGF.

CONCLUSION

Ad-ING4-IL-24 had an enhanced radiosensitivity effect on human lung adenocarcinoma, and therefore acted as a radiotherapy sensitizer, which may be related to its effect on apoptosis-induction and antiangiogenesis.