title: Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma.
abstract: In numerous types of cancer, the expression of a novel member of the B7 ligand family, the B7-H3 immunoregulatory protein, has been correlated with a poor prognosis. In the present study, we investigated the role of B7-H3 in chemoresistance in pancreatic carcinoma. Silencing of B7-H3, through lentivirus-mediated delivery of stable short hairpin RNA, was observed to increase the sensitivity of the human pancreatic carcinoma cell line Patu8988 to gemcitabine as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 caused the cancer cells to be more resistant to the drug. Subsequently, we investigated the underlying mechanisms of B7-H3-mediated gemcitabine resistance, and found that the levels of survivin decreased in cells in which B7-H3 had been knocked down. In vivo animal experiments demonstrated that tumors in which B7-H3 had been knocked down displayed a slower growth rate compared with the control xenografts. Notably, gemcitabine treatment led to a strong antitumor activity in mice with tumors in which B7-H3 had been knocked down; however, this effect was only marginal in the control group. Furthermore, survivin expression was weak in gemcitabine-treated tumors in which B7-H3 had been knocked down and apoptosis was increased, as revealed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining. In summary, the present study demonstrated that B7-H3 induces gemcitabine resistance in pancreatic carcinoma cells, at least partially by downregulating survivin expression. These results provide novel insights into the function of B7-H3 and encourage the design and investigation of approaches targeting this protein in treating pancreatic carcinoma.
authors: Departments of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006,  P.R. China.
authors: Xin
authors: X
authors: Zhao
authors: Guang-Bo
authors: GB
authors: Zhang
authors: Wen-Juan
authors: WJ
authors: Gan
authors: Feng
authors: F
authors: Xiong
authors: Zhi
authors: Z
authors: Li
authors: Hua
authors: H
authors: Zhao
authors: Dong-Ming
authors: DM
authors: Zhu
authors: Bin
authors: B
authors: Zhang
authors: Xue-Guang
authors: XG
authors: Zhang
authors: DE-Chun
authors: DC
authors: Li
keywords: B7-H3; chemoresistance; pancreatic carcinoma; shRNA