P R A C E O R Y G I N A L N E
ginekologia
Quercetin inhibits proliferation and increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel
Kwercetyna hamuje proliferację i zwiększa wrażliwość komórek raka jajnika na cisplatynę i paklitaksel
Adam Maciejczyk
13aZeá 6XURZiak
21 Lower Silesian Centre of Oncology, Wroclaw, Poland
² Department of Histology and Embryology, University School of Medicine, Wroclaw, Poland
Abstract
Introduction: Due to frequent diagnosis of ovarian cancer at an advanced clinical stage, in most cases surgical debulking is followed by chemotherapy. The principal cause of therapeutic failure involves incomplete surgery and resistance of neoplastic cells to chemotherapy. A search continues for substances which would overcome resistan- ce to treatment and, as a result, would increase efficacy of the applied treatment. Quercetin represents one of more interesting compounds, which at present in subjected to several tests.
Material and methods: Studies were performed on in vitro sensitivity of human ovarian cancer cell lines, SKOV-3, EFO27, OVCAR-3 and A2780P to low doses of quercetin and on the effect exerted by quercetin on sensitivity of the cell lines to cisplatin and pactitaxel.
Results: The experiments proved that the studied cells of ovarian cancer manifest a similar sensitivity to quercetin.
Following incubation of the cells with two distinct concentrations of quercetin and the studied cytostatic agents all the cells lines were found to significantly increase their sensitivity to pactitaxel In cases of two cell lines, OVCAR-2 and A2780P, they also significantly increased their sensitivity to cisplatin.
Discussion: Our results demonstrated suitability of low quercetin doses (achievable using oral administration) as a substance which increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel. The value of quercetin include its wide accessibility, efficacy and a broad range of activity but also its low toxicity, as compared to other examined compounds.
Conclusions: Used in low doses, quercetin increases chemosensitivity of ovarian cancer cells
Key words: quercetin / ovarian cancer / cisplatin / paclitaxel / chemoresistance /
Otrzymano: 06.03.2013
Zaakceptowano do druku: 10.06.2013 Address for correspondence:
Paweł Surowiak,
Department of Histology and Embryology, University School of Medicine ul. Chałubińskiego 6a, 50-356 Wrocław, Poland
phone: +48-71-7841355; Fax: +48-71-7840082 e-mail: pawel.surowiak@interia.pl
Introduction
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Aim of study
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Material and methods
Cell lines and cell cultures
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Wstęp: Ze względu na częste rozpoznawanie raków jajnika w zaawansowanym stadium klinicznym w większości przypadków po przeprowadzeniu zabiegu operacyjnego stosowana jest chemioterapia. Podstawową przyczyną niepowodzeń stosowanej terapii jest nieradykalność leczenia operacyjnego oraz oporność komórek nowotworo- wych na chemioterapię. Poszukuje się substancji, które pozwolą zwalczyć oporność na leczenie i w efekcie zwięk- szyć skuteczność stosowanej terapii. Jednym z ciekawszych związków poddawanych obecnie szeregowi badań jest kwercetyna.
Materiał i metody: Przeprowadzono badania in vitro wrażliwości linii komórkowych ludzkiego raka jajnika SKOV-3, EFO27, OVCAR-3 i A2780P na niskie dawki kwercetyny oraz ocenę wpływu kwercetyny na wrażliwość linii komór- kowych na cisplatynę i paklitaksel.
Wyniki: Przeprowadzone doświadczenia wykazały, że badane komórki raka jajnika wykazują zbliżoną wrażliwość na kwercetynę. W wyniku inkubacji badanych komórek z dwoma różnymi stężeniami kwercetyny i z badanymi cyto- statykami wykazaliśmy, że wszystkie linie istotnie zwiększyły swoją wrażliwość na paklitaksel. W przypadku dwóch linii – OVCAR-2 i A2780P uzyskaliśmy również istotny wzrost wrażliwości na cisplatynę.
Dyskusja: Nasze badania wykazały przydatność niskich dawek kwercetyny (osiągalnych przy podaży doustnej), jako substancji zwiększającej wrażliwość komórek raka jajnika na cisplatynę i paklitaksel. Jej walory podkreśla nie tylko łatwa dostępność, skuteczność i szeroki zakres działania, ale również mała, w porównaniu z innymi badanymi substancjami, toksyczność.
Wnioski: Kwercetyna zastosowana w niskich dawkach powoduje wzrost chemiowrażliwości komórek raka jajnika
Słowa kluczowe: kwercetyna / rak jajnika / cisplatyna / paklitaksel / chemioopornoĞü /
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Evaluation of quercetin toxicity
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Evaluation of quercetin effect on cell sensitivity to cisplatin and paclitaxel
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Results
Toxicity of quercetin toward ovarian cancer cells
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Evaluation of quercetin effect on cell sensitivity to cisplatin and paclitaxel
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Ta b l e I . Sensitivity of various ovarian cancer cell lines to paclitaxel and cisplatin in therapeutic concentrations (K2) expressed in percentages of control cell numbers.
Paclitaxel (0.29 x 10-5 ȝ0 [% control]
Cisplatin (16.66 x 10-5 ȝ0 [% control]
SKOV-3 100 21
EFO27 98 34
OVCAR-3 76 38
A2780P 61 12
Ta b l e I I . Coefficients of statistical significance for comparisons of quercetin effects in concentration of 1 or 5 μM on cell line sensitivity to paclitaxel and cisplatin as compared to the control (test U of Mann-Whitney).
5ȝ0 TXercetin 1ȝ0 TXercetin 5ȝ0 TXercetin 1ȝ0 TXercetin
SKOV-3 <0.001 0.04 >0.05 >0.05
EFO27 >0.05 0.002 >0.05 >0.05
OVCAR-3 0.007 >0.05 <0.001 >0.05
A2780P <0.001 <0.001 0.03 >0.05
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Figure 1. Effect of quercetin on survival of studied ovarian cancer cells. Figure 4. Comparison of OVCAR-3 cell line sensitivity to paclitaxel and cisplatin supplemented without or with 1 or 5 μM quercetin. Results are presented in percentages of the control with medium alone.
Figure 2. Comparison of SKOV-3 cell line sensitivity to paclitaxel and cisplatin used without or with 1 or 5 μM quercetin. Results represent percentages of the control with medium alone.
Figure 5. Comparison of A2780P cell line sensitivity to paclitaxel and cisplatin supplemented without or with 1 or 5 μM quercetin. Results are presented in percentages of the control with medium alone.
Figure 3. Comparison of EFO27 cell line sensitivity to paclitaxel and cisplatin supplemented without or with 1 or 5 μM quercetin. Results presented in percentages of the control with medium alone.
Discussion
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R e f e r e n c e s
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International Society of Ultrasound in Obsterics & Gynecology
Ultrasound Section of Polish Society of Gynecology
––––––––––––––––––––––––––––
International Society of Ultrasound in Obsterics & Gynecology – ISUOG
o r a z
Sekcja USG PTG
zapraszają
w dniach
06-07.09.2013
n a K u r s
Fetal malformation
prezentacja przypadków live, tłumaczenia symultamiczne
––––––––––––––––––––––––––––
W y k ł a d ow c y :
Członkowie ISUOG za całej Europy
K i e row n i k Kurs u :
Marek Dubiel (ISUOG – Polska) Marek Pietryga (ISUOG – Polska)
M i e j s c e o b ra d :
Toruń
Hotel Bulwar, ul. Bulwar Filadelfijski
Z g ł o s z e n i a
w w w. r e g o m e d . p l
t e l . 6 6 3 0 6 4 0 0 0
Uczstnicy Kursu otrzymają certyfikat uczestnictwa
International Society of Ultrasound in Obsterics & Gynecology – ISUOG
oraz
30 punktów edukacyjnych USG PTG
K O M U N I K AT
