JOURNAL ARTICLE

Arsenic trioxide suppresses thymidylate synthase in 5-FU-resistant colorectal cancer cell line HT29 In Vitro re-sensitizing cells to 5-FU

Pochi Ramalingam Subbarayan, Kelvin Lee, Bach Ardalan
Anticancer Research 2010, 30 (4): 1157-62
20530422
Identification of new agents with antitumor activity in chemoresistant tumors is urgently needed for the treatment of colorectal cancer. Arsenic trioxide (As(2)O(3)), a Food and Drug Administration (FDA) approved drug is successfully being used to treat acute promyelocytic leukemia (APL). Several clinical trials also suggest its ineffectiveness on solid tumors. We proposed that arsenic trioxide may be used as chemosensitizer, especially to 5-fluorouracil (5-FU). The effect of arsenic trioxide on cell proliferation of 5-FU-sensitive and -resistant HT29 colorectal cancer cells in vitro was tested by trypan blue dye exclusion assay, 2, 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-S-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) cell proliferation assay and cell cycle analysis using flow cytometry. Gene expression was analyzed using real-time polymerase chain reaction (PCR) and Western blot methods. There was a dose-dependent increase in cell detachment and proliferation in HT29 and HT29FU cells. As a single agent, arsenic trioxide also down-regulated thymidylate synthase (TS) expression without affecting the expression of some other genes analyzed in the above cell lines. Combination of arsenic trioxide and 5-FU increased cytotoxicity. In vitro data show that as a single agent, arsenic trioxide down-regulated TS expression in HT29 cells. Addition of 5-FU to these sensitized cells increased cytotoxicity. These findings open up a possibility to use arsenic trioxide as a chemosensitizer in combination therapy.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
20530422
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"