Sensitization of tumor to ²¹²Pb radioimmunotherapy by gemcitabine involves initial abrogation of G2 arrest and blocked DNA damage repair by interference with Rad51.

ABSTRACT:

Purpose

To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using (212)Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers.

Methods and materials

Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by (212)Pb-TCMC-trastuzumab and compared with controls.

Results

Treatment with (212)Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). (212)Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation

SUBMITTER: Yong KJ 

PROVIDER: S-EPMC3594422 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature