title: Weakening Impact of Excessive Human Serum Albumin (eHSA) on Cisplatin and Etoposide Anticancer Effect in C57BL/6 Mice with Tumor and in Human NSCLC A549 Cells.
abstract: Excessive human serum albumin (eHSA) impact on anticancer effects is inconsistent. We explored the outcome of cisplatin (DDP)/etoposide (VP-16) plus eHSAin vivoandin vitro. C57BL/6 mice with tumor were used to compare the efficacy of DDP/VP-16 alone and DDP/VP-16+eHSA. Blood albumin was measured to confirm whether eHSA elevate its level. Western blotting assay were used to measure the expression of ERCC1/TOP2A in tumor tissues. Cell proliferation, mRNA, and protein expression of ERCC1/TOP2A were also assayed to compare two groups in A549 cells. Furthermore we evaluated eHSA impact on cell proliferation in RNAi targeting ERCC1/TOP2A in A549 cells, respectively. eHSA reduced the anticancer effect of DDP/VP-16 without altering albumin level, increased protein expression of ERCC1/TOP2A, respectively in mice. Similarly, eHSA increased mRNA and proteins expression of ERCC1/TOP2A in A549 cells. In RNAi A549 cells, however, eHSA no longer weakened but enhanced the anticancer effect of DDP, while no longer altered the effect of VP-16. Our findings suggested that eHSA weaken the anticancer effect of DDP/VP-16 via up-regulating ERCC1/TOP2A expression, respectively. Further molecular mechanism studies are warranted to investigate whether eHSA is not conducive to lung cancer chemotherapy.
authors.affiliation: Fengxian Hospital Graduate Training Base, Jinzhou Medical UniversityShanghai, China; Graduate School, Jinzhou Medical UniversityLiaoning, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Fengxian Hospital, Southern Medical University Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Graduate School, Jinzhou Medical University Liaoning, China.
authors.forename: Yuanchi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, Fengxian Hospital, Southern Medical University Shanghai, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Li
authors.affiliation: Rutgers Cancer Institute of New Jersey, The State University of New Jersey New Brunswick, NJ, USA.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Tan
authors.affiliation: Fengxian Hospital Graduate Training Base, Jinzhou Medical UniversityShanghai, China; Department of Pharmacy, Fengxian Hospital, Southern Medical UniversityShanghai, China; Department of Pharmacy, 6th People's Hospital South Campus, Shanghai Jiaotong UniversityShanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
keywords: A549; C57BL/6 mice; cisplatin; etoposide; human serum albumin