title: Blockade of PI3K/AKT pathway enhances sensitivity of Raji cells to chemotherapy through down-regulation of HSP70.
abstract: Up-regulation of heat shock protein 70 (HSP70) could be elicited primarily by heat in former studies, and this was proved to be associated with cancer progression. Burkitt's lymphoma is one of highly aggressive B-cell non-Hodgkin's lymphoma and is one of the fastest growing human tumors. To investigate the effect of HSP70 expression on the sensitivity of human Burkitt lymphoma cells (Raji cells) to chemotherapy and its role in the involvement of PI3K/AKT pathway, we evaluated the effects of LY294002, a PI3K inhibitor, on the expression of HSP70 and cell sensitivity to adriamycin (ADM) or cisplatin (DDP). In present study, expressions of HSP70, AKT and phosphorylated AKT (p-AKT) in Raji cells were measured by Western-Blot. Apoptosis index of Raji cells was examined by flow cytometry. Cytotoxicities of adriamycin (ADM) and cisplatin (DDP) were determined by WST-8 assay. We found that hyperthermia (42 degrees for 1 hour) up-regulated the expression of HSP70 expression and blockade of PI3K/AKT pathway down-regulated HSP70 expression in Raji cells. Compared to cells treated with ADM or DDP alone, hyperthermia protected cells from chemotherapy while LY294002 enhanced sensitivity of Raji cells to chemotherapy. Our results suggested down-regulation of HSP70 expression by blockade of PI3K/AKT pathway maybe responsible for the increased sensitivity of Raji cells to chemotherapy. Targeting PI3K/AKT pathway or inhibiting HSP70 expression may be beneficial for chemotherapy treatment of Burkitt lymphoma patients.
authors.affiliation: Department of Hematology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, P,R, China. xinwang55@yahoo.com.cn.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Fang
authors.forename: Yujie
authors.initials: Y
authors.lastname: Jiang
authors.forename: Lili
authors.initials: L
authors.lastname: Feng
authors.forename: Haiping
authors.initials: H
authors.lastname: Chen
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhen
authors.forename: Mei
authors.initials: M
authors.lastname: Ding
authors.forename: Xin
authors.initials: X
authors.lastname: Wang