Mitosene유사체의 난소암세포주 성장억제에 관한 연구
In Vifro Growth Inhibition of Human Ovarian Cancer Cell Lines by Mitosene Analogues
대한암학회지 1997년 29권 3호 p.437 ~ 444
소속 상세정보
차동수/Dong Soo Cha
김수기/안찬묵/최선주/박윤선/한상원/안찬묵/Soo Kie Kim/Chan Mug Ahn/Sun Ju Choi/Yoon Sun Park/Sang Won Han/Chan Mug Ahn
KMID : 0360319970290030437
Abstract
목적 : 마이토센 유사체의 인체 난소암세포주에 대한 세포독성 및 클론 형성저지율을 측
정하고 세포주기에 미치는 영향을 조사하여 실험적 난소암 치료제로서의 가능성을 알고자
하였다.
재료 및 방법 : 본 연구소에서 합성한 마이토센유사체를 인체 난소암세포주인 SK-OV3,
SW-626에 처치하여, 항암활성 측정은 MTT법 및 끌론 형성법을 사용하였고, 세포주기측
정을 위하여 유식세포측정을 시행하였다.
결과 : 5개의 마이토센 유사체들을 합성하였고, 이 화합물을 시험관내에서 인체 난소암세
포주에 처리하였을 때 대체로 대조약물(mitomycin C, cisplatin, 5-fluorouracil, taxol,
adriamycin 및 etoposide 등)에 비교하여 비슷한 시험관내 세포독성 및 종양클론 형성억제
율을 보였으며 또한 유식세포분석에서 22번 화합물을 처리하였을 때(10 ㎍/ml) 약물 비처리
세포군 및 taxol처리 세포군에 비하여 다른 세포주기 모양을 보였다.
결론 : 마이토센 유사체들은 인체 난소암세포주에 대하여 우수한 성장저지능을 보였으며
유식세포분석에서 마이토센 유사체처리(10 ㎍/ml) 세포들은 기존 약제와는 다른 세포주기
양상을 나타내었다.
#초록#
Ovarian cancer is the 3rd most common type of gynecological cancer among women
in Korea. With this high incidence, epithelial ovarian cancer has been often diagnosed as
advanced disease with more than 60% of the patients presenting in stage Ⅲ or IV. As
a mean to overcome ovarian cancer, cytoreductive surgery and chemotherapy have been
the mainstay of its treatment. Currently, various forms of adjuvant therapy such as
immunotherapy, radioactive chromic phosphate administration have been developed.
Nevertheless, these therapeutic strategies little contribute to remarkable improvement of
survival in cancer patient. Untill yet, the most apparopriate adjuvant therapy is unknown
and no single mode of adjuvant therapy appears to be superior to others. Currently, for
the treatment of stage Ⅲ or higher, chemotherapy was reported to be the most
effective. Among several chemotherapy regimen, cisplatin-based chemotherapy remains
the mainstay of adjuvant tratment in early-stage, just as it does in advanced ovarian
carcinoma. In clinical field, some alkylating agents mitomycin C, cyclophosphamide also
have been introduced to treat various stage of ovarian cancer patients in a combined
regimen. However, the combined chemotherapy using alkylating agents has been limited
in their usefulness owing to their high toxicity. Therefore, the development of effective
chemotherapeutic for the treatment of ovarian cancer will be warranted. To reduce
toxicity of alkylating quinones and optimize their activity, mitosene was proposed as one
of promising candidate. This compound had an action of reductive alkylating quinone.
Alkylating quinone methides which are formed upon reduction of the quinones and
subsequent elimination of leaving groups are highly reactive and produce cytotoxic
effects by reacting with DNA(nucleophile) of tumor cells. Because tumor cells possess a
low reduction potential environment, reductive alkylating quinones, such as mitosene
analogues may be hypothesized to selectively target hypoxic tumor cells. Recently, some
clinical studies using mitosene analogues, designed as new DNA cross-linkers,
mimicking mitomycin C were reported to show potent cytostatic activity. However, there
is few reports on the inhibition of ovarian cancer cell line by mitosene analogues.
Therefore it is important to judge on whether mitosene analogues can be applied in the
chemotherapy of ovarian cancer. Thus, the present study was directed to evaluate if
mitosene analogues not only inhibit a growth, colony forming ability of human ovarian
cancer cells and but also cause a change of cell cycle pattern.
키워드
원문 및 링크아웃 정보
등재저널 정보