The Effect Of Plumbagin Downregulated Glut-1 Expression On Tumor Biological Behavior And Anti-cancer Therapy

Tongue squamous cell carcinoma(TSCC)is a very common cancer in the malignancy of head and neck.The oncogenetic and developmental mechanism of TSCC is not fully understood and there is lack of effective therapies.Recently,more and more researchers focus on the study between tumor and energy metabolism.As Oncomine data showed,glucose transporter 1(Glut-1)is overexpression in many cancers,resulting in high level of glucose metabolism and rapid proliferation of tumor cells,which suggests that Glut-1 plays a key role in behaviors of tumor biology.However,there are less reports on Glut-1 and tumor invasion and metastasis,particularly the effect on TSCC.Plumbagin(PLB)is isolated from the root of Plumbago zeylanica L and it possesses anti-cancer,anti-inflammation,and anti-oxidant activities.In our previous studies,we found that PLB significantly inhibited PI3K/Akt signaling pathway,activated NF-κB signaling pathway,promoted p53 expression level,and generated a lot of ROS for killing cancer cells.But it is unknown if PLB kills TSCC cells via mediating energy metabolism.Here,we analyzed the Glut-1 and MMP-2 expression and location in 45 clinical samples,examined the expression level of Glut-1 and the effect on behaviors of tumor biology after PLB treatment,and further elaborated the mechanism that PLB inhibits Glut-1 expression.Our results included:(1)Glut-1 and MMP-2 expression are relative to the invasion and metastasis of TSCC and clinical stages;(2)PLB significantly suppressed the proliferation,glucose metabolism,and migration and invasion of TSCC CAL27 cells;(3)PLB inhibited Glut-1 expression via mediating PI3K/Akt pathway and p53-independent pathway;(4)In TSCC CAL27 xenograft model,PLB effectively suppressed growth of CAL27 tumor and inhibited the expression level of Glut-1,MMP-2,CD31,and Ki67 compared with control group in vivo.To sum up,we elaborated the effect of Glut-1 on rapid growth,invasion and metastasis of TSCC and the mechanism that PLB treats TSCC through downregulating Glut-1 expression.It supplies theoretical basis for PLB pharmaco-therapy in clinical.