Correlative nanomechanical profiling with super-resolution F-actin imaging reveals novel insights into mechanisms of cisplatin resistance in ovarian cancer cells.
The exact molecular mechanisms of ovarian cancer platinum resistance are not well understood, and biomarkers to reliably predict ovarian cancer resistance to platinum and other chemotherapeutic agents are lacking. Biomechanics of cisplatin-treated ovarian cancer cells were measured quantitatively at nanoscale level using atomic force microscopy. We demonstrate that cisplatin modulates the cellular nanomechanics of ovarian cancer cells; sensitive cells show dose-dependent increase in cell stiffness, which is effected by disrupting the F-actin polymerization. In contrast, resistant cells show no significant changes in cell stiffness upon cisplatin treatment. Further, stimulated emission depletion, an emerging super-resolution microscopy, shows that at the molecular level, F-actin is indeed remodeled considerably in cisplatin-sensitive and cisplatin-resistant cells. These findings reveal a direct role of the actin remodeling mechanism in cisplatin resistance of ovarian cancer cells, suggesting potential future applications of nanomechanical profiling as a marker for cancer drug sensitivity.


BACKGROUND
In this paper, nanomechanical profiling and an emerging super-resolution microscopy method was utilized to decipher the mechanisms of cisplatin resistance in ovarian cancer cells, paving the way to future studies of this and similar other problems with drug resistance in cancer biology.
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA. sharmas@ucla.edu
Shivani
S
Sharma
Chintda
C
Santiskulvong
Laurent A
LA
Bentolila
JianYu
J
Rao
Oliver
O
Dorigo
James K
JK
Gimzewski
D008841:Actin Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D000199:Actins / Q000737:chemistry / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018625:Microscopy, Atomic Force; D010051:Ovarian Neoplasms / Q000188:drug therapy; D058105:Polymerization
D000199:Actins; D002945:Cisplatin