Combined inhibition of Chk1 and Wee1 paper

Question 1

how were genes identified that have synthetic lethality with chk1?

Answer 1

• high throughput screening using a siRNA library directed against 719 human protein kinases in human ovarian cancer cell line OVCAR-5 (resistant to Chk1 inhibitors)

Question 2

what was identified to have synthetic lethality with chk1?

Answer 2

Wee1 kinase

Question 3

what effects does adding non-toxic concentrations of a chk1 and a wee1 inhibitor have on cancer cells?

Answer 3

Chk1 and wee1K inhibitors have a synergestic effect in human cancer cells - reduced viability to <50%

• co-treatment had marked cytotoxic activity
• treatment with only 1 agent - limited cytotoxic activity

Question 4

what type of mitosis does combined treatment with Week inhbitor and chk1 inhibitor cause in cancer cells?

Answer 4

• premature mitosis before the end of DNA replication

- results in apoptosis of these cells

Question 5

what was the in vivo effect of combined treatment with chk1 inhibitor and wee1k inhibitor?

Answer 5

High anti-tumour effect is mouse treated with both agents,

Question 6

What do FACs and biparametric analysis show about cells treated with chk1 and wee1k inhibitors?

Answer 6

• cells do not express specific markers of S and G phases
• cells do not incorperate BrDu - no undergoing active cell division/ DNA replication
• cells accumu,kated that were not in an active replication stage - were between 2N and 4N