Effects of gemcitabine on radiosensitization, apoptosis, and Bcl-2 and Bax protein expression in human pancreatic cancer xenografts in nude mice

Abstract

ABSTRACT. The aim of this study was to evaluate the radiosensitizing effects of gemcitabine towards human pancreatic cancer xenografts. A human pancreatic cancer xenograft model was established in nude mice, 36 of which were randomly divided into 6 treatment groups. Tumors were measured every 2 days, and the tumor volumes, growth delays, and inhibition rates were compared to evaluate the gemcitabine enhancement factor. The apoptotic index was determined by terminal deoxynucleotidyl transferase dUTP nick end-labeling assay, and apoptosis inhibitory protein Bcl-2 and apoptosis-related protein Bax expression were detected by immunohistochemistry. Compared with the control group, xenograft growth was significantly inhibited in the 25 (G25) and 50 mg/kg gemcitabine (G50) groups (P < 0.05). In the 25 (G25R) and 50 (G50R) mg/kg gemcitabine + radiotherapy groups, local tumor growth was significantly inhibited, with inhibition rates of 88.22 and 91.23%, respectively, significantly higher than those of (2015) the simple radiotherapy (SR), G25, and G50 groups (44.11, 72.88, and 77.53%, respectively; P < 0.05). The tumor growth delay in the G25R and G50R groups were 9 and 15 days, respectively, higher than the SR, G25, and G50 groups (each 4 days, P < 0.05). The apoptosis of tumor cells in the intervention groups significantly increased, and the apoptotic index among the intervention groups exhibited significant differences (P < 0.05). The immunohistochemical results indicated that Bcl-2 was downregulated to different degrees in the intervention groups, whereas Bax was upregulated (P < 0.05). Therefore, gemcitabine appears to enhance the radiotherapeutic sensitivity of human pancreatic cancer xenografts significantly.

Cuscuta chinensisflavonoids alleviate bisphenol A‐induced apoptosis of testicular cells in male mice offspring

“…B‐cell leukaemia/lymphoma‐2 family can be divided into anti‐apoptotic proteins and pro‐apoptotic proteins (Cory & Adams, ). Bcl‐2 and bax are the most representative proteins in Bcl‐2 family (Ghasemi et al, ; Shen, Wu, Wang, Li, & Zhu, ; Tenorio, Santana, Queiroz, Oliveira, & Queiroz, ), one inhibits apoptosis and the other promotes apoptosis, respectively, and play an important role in apoptosis induced by bisphenol A (Gong et al, ). There is a strong negative correlation between bax and bcl‐2, which is the main regulator of bcl‐2 activity.…”

The Effect of Radiosensitization of Gemcitabine Related to Suppression of a Repair Pathway: Examination of Mammalian Cells with Therapeutic High Energy X-rays

“…Additionally, it is one of the more effective drugs for sensitization of cells to radiation, because most pancreatic cancers do not respond to gemcitabine alone [1][2][3][4]. The radiosensitizing properties of gemcitabine have been demonstrated both in vivo and in vitro [5][6][7][8][9][10][11][12][13], although the detailed interaction of gemcitabine with radiation has not been elucidated. In preliminary experiments with human lung carcinoma cells, van Putten et al showed that gemcitabine treatment retards the rate and extent of DNA double-strand break (DSB) repair [14].…”