Effects of salidroside on glioma formation and growth inhibition together with improvement of tumor microenvironment

Abstract

Objective: To test the effects of salidroside on formation and growth of glioma together with tumor microenvironment.

Methods: Salidroside extracted from Rhodiola rosea was purified and treated on human glioma cells U251 at the concentration of 20 µg/mL. 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide (MTT) assay for cytotoxicity and flow cytometry (FCM) for cell cycle analysis were performed. Then for in vivo study, xenotransplantation tumor model in nude mice was generated and treated with salidroside at the concentration of 50 mg/kg(.)d for totally 20 d. Body weight and tumor size were detected every 2 d after the treatment. The levels of 8-isoprostane, superoxide dismutase (SOD) and malondialdehyde (MDA), special markers for oxidative stress, were detected while immunofluoresence staining was performed for astrocyte detection.

Results: For in vitro study, salidroside could decrease the viability of human glioma cells U251 and the growth of U251 cells at G0/G1 checkpoint during the cell cycle. For in vivo study, salidroside could also inhibit the growth of human glioma tissue in nude mice. The body weight of these nude mice treated with salidroside did not decrease as quickly as control group. In the tumor xenotransplantation nude mice model, mice were found of inhibition of oxidative stress by detection of biomarkers. Furthermore, overgrowth of astrocytes due to the stimulation of oxidative stress in the cortex of brain was inhibited after the treatment of salidroside.

Conclusions: Salidroside could inhibit the formation and growth of glioma both in vivo and in vitro and improve the tumor microenvironment via inhibition of oxidative stress and astrocytes.

Keywords: Glioma; astrocyte; cell cycle; cytotoxicity; oxidative stress; salidroside; tumor microenvironment; xenotransplantation.

Figure 1

Cell viability test by MTT. *, P<0.05, compared with the negative control group.

Figure 2

The body weight of nude mice (N=10).

Figure 3

The size of xenotransplanted tumor in negative control group and salidroside group (N=10).

Figure 4

Analysis on the ROS relative enzymes in the cortex of nude mice brain. (A) 8-isoprostane; (B) SOD; (C) MDA. *, P<0.05, compared with the negative control group.

Figure 5

Growth of astrocytes (arrow indicated) near the ventricle of nude mice brains (200×). (A) Overgrowth of astrocytes in negative control group; (B) Inhibition of overgrowth of astrocytes in salidroside group. Bar, 50 µm.

Figure 6

Analysis on formation of astrocytes. *, P<0.05, compared with the negative control group.