JOURNAL ARTICLE

Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells

Vasileios A Stamelos, Elizabeth Robinson, Charles W Redman, Alan Richardson
Gynecologic Oncology 2013, 128 (2): 377-82
23168176

OBJECTIVES: To evaluate the efficacy of combination of navitoclax, carboplatin and paclitaxel in ovarian cancer.

METHODS: 8 ovarian cancer cell lines were treated with either doublet or triplet combinations of navitoclax, carboplatin and paclitaxel. Interactions were assessed by determining a combination index or measuring caspase activity. The effect of the combinations was also evaluated by measuring the inhibition of cells grown as spheroids.

RESULTS: Navitoclax exhibited modest (IC(50)=3-8 μM) single agent potency. Antagonism between carboplatin and paclitaxel was evident in Ovcar-4, Ovcar-8 and Skov-3 cells. Drug combinations including navitoclax with carboplatin and/or paclitaxel showed significantly less antagonism, or even synergy, in several cell lines than carboplatin/paclitaxel alone. Navitoclax enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells. Combinations of navitoclax, carboplatin and paclitaxel showed more than additive activity against Igrov-1 spheroids.

CONCLUSIONS: Navitoclax improves the activity of combinations of carboplatin and paclitaxel in vitro. Our observations, taken with other published data, provide a rationale for clinical trials of navitoclax in ovarian cancer in combination with chemotherapy.

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
23168176
×

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"