title: Increased chemocytotoxicity to colon cancer cells by shock wave-induced cavitation.
abstract: OBJECTIVE
  Cavitation has been shown to hinder colon cancer cell proliferation in vitro. This study aimed at investigating the interest of combining cavitation and cytotoxic drugs in vitro.
  
  
  METHODS
  HT-29 cells were exposed in suspension to cavitation (shock waves plus bubbles) before 5-fluorouracil (FUra) administration. Cytotoxicity was studied by means of clonogenic survival, cell proliferation by [3H]deoxyuridine ([3H]dUdR) incorporation, and influence of the treatments on the cell cycle by cytofluorimetry; the effects of cavitation on RNA incorporation of FUra, cell permeability, and activity of thymidilate synthetase (TS) were also studied.
  
  
  RESULTS
  A preliminary exposure to cavitation (as compared with FUra alone) induced decreased colony formation (by up to 2 log in certain conditions) and colony size. Cavitation alone induced increased incorporation of [3H]dUdR during 48 hours and stimulated TS activity, but in the presence of FUra, the concentration of the drug that causes 50% inhibition of control cell growth for [3H]dUdR incorporation was reduced by up to 1 log, and TS inhibition was increased after cavitation as compared with FUra alone. RNA incorporation of [14C]FUra was increased by cavitation, as a consequence of altered cell permeability rather than a direct RNA effect. Seventy-two hours after treatment, cavitation plus FUra decreased by more than 50% the S-phase fraction and also inhibited mitosis.
  
  
  CONCLUSIONS
  Submitting HT-29 cells to cavitation before treatment by FUra significantly increases the effects of the drug. The action of both agents appears to be partially synergistic with a cycle specificity.
authors.affiliation: INSERM U 281, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Prat
authors.forename: A
authors.initials: A
authors.lastname: Sibille
authors.forename: C
authors.initials: C
authors.lastname: Luccioni
authors.forename: D
authors.initials: D
authors.lastname: Pansu
authors.forename: J Y
authors.initials: JY
authors.lastname: Chapelon
authors.forename: J
authors.initials: J
authors.lastname: Beaumatin
authors.forename: T
authors.initials: T
authors.lastname: Ponchon
authors.forename: D
authors.initials: D
authors.lastname: Cathignol
mesh_terms: D000388:Air; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003857:Deoxyuridine / Q000378:metabolism; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008863:Microspheres; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D013940:Thymidylate Synthase; D005472:Fluorouracil; D003857:Deoxyuridine