Anti-glioma Effect And Mechanism Of Marine Drug HPN Combined With Temozolomide

Glioma is the most common malignant tumor in central nervous system.Chemotherapy is an important adjuvant therapy of glioma.In chemotherapy,alkylating drugs,such as temozolomide(TMZ),is used frequently.Due to the lack of targeting and toxic side effects of conventional chemotherapy drugs,the study of molecular targeted therapy of glioma has become a hot spot.However,it has been found that the single-use of molecular targeted drugs is not obvious in curative effect.Before the development of better targeted drugs,the combination of targeted drugs and conventional chemotherapy drugs has shown promising prospects.In our lab,3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-(isopropoxymethyl)benzyl)benzene-1,2-diol(HPN)was obtained by modifying the structure of a extract from marine plant Rhodomela confervoides.In vitro cytological experiments,it showed that HPN had good antitumor activity in human glioma U87 cell line and its IC50 was 6.7?mol/L.In vitro enzymatic experiments,it showed that HPN had a good inhibitory activity against protein tyrosine phosphatase 1B(PTP1B),and its IC50 reached 0.63?mol/L.At the same time,HPN showed good targeting to PTP1 B.In this study,the effect and mechanism of marine drug HPN combined with temozolomide on glioma was investigated.The results of MTT showed that the combination of low-dose HPN and TMZ could significantly enhance the anti-glioma activity of TMZ.Cell scratch test and transwell chamber assay revealed that the combination of HPN and TMZ could significantly inhibit the migration and invasion of U87 cells.Annexin V/PI double staining and western-blot showed that the combination of HPN and TMZ could promote the apoptosis of U87 cells.In further studies,we found HPN could decrease the expression level of p-src,p-fak,p-STAT3,p-Akt and p-ERK in U87 cells.Through the detection of tumor tissue samples obtained from clinic,it was found that the expression of PTP1 B in glioma tissues was significantly higher than that in the para-tumor tissues.Therefore,we hypothesized that HPN may decrease the expression level of p-src,p-fak,p-STAT3,p-Akt and p-ERK by targeted inhibiting of PTP1 B,and then exerted the anti-glioma effect.PTP1 B may be a new target for molecular targeted therapy of glioma.