267 ²ÔÍ íàëåaeàòü äî ðîäèíè öèòîê³í³â, ÿê³ ³íäóêóþòü íåñïåöèô³÷íó ðåçèñòåíòí³ñòü â êë³òèíàõ äî ð³çíèõ â³ðóñ³â. Ðàçîì ç òèì, ö³ á³ëêè ïðèãí³÷óþòü ïðîë³ôåðà-ö³þ íîðìàëüíèõ òà ïóõëèííèõ êë³òèí, ðåãóëþþòü ð³âåíü ¿õ äèôåðåíö³þâàííÿ, à òàêîae ìîäóëþþòü in vivo àê-òèâí³ñòü ð³çíèõ êîìïîíåíò³â ³ìóííî¿ ñèñòåìè. Ñàìå ö³ âëàñòèâîñò³ ²ÔÍ ïðèâåðòàþòü óâàãó îíêîëîã³â [1, 19]. Ðåçóëüòàòè åêñïåðèìåíòàëüíèõ äîñë³äaeåíü òà êë³í³÷íèé äîñâ³ä ñâ³ä÷àòü, ùî íàéá³ëüø âèðàaeåíèé ïðîòèïóõëèííèé åôåêò âèÿâëÿþòü ²ÔÍ ó

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... íàö³¿ ç öèòîñòàòèêàìè àáî ç ³íøèìè öèòîê³íàìè, â òîìó ÷èñë³ ç ÔÍÏ [2, 17, 24], àëå ìåõàí³çìè ï³äâèùåííÿ àêòèâ-íîñò³ òàêî¿ êîìá³íàö³¿ äîñ³ íåäîñòàòíüî âèâ÷åí³. ³äîìî, ùî åôåêòèâí³ñòü ïðîòèïóõëèííî¿ òåðàﳿ çíà÷íîþ ì³ðîþ âèçíà÷àºòüñÿ ð³âíåì âèíèêíåííÿ â Interferon alpha (IFN) has been shown to increase in vitro cytotoxicity of anticancer agents, in particular tumor necrosis factor (TNF) and vinblastin (VBL), on tumor cell lines (U-937, K-562, HEp-2). This effect seems to be due to IFN ability to enhance apoptosis resulting in increasing number of apoptotic cells and increasing oligonucleosomal DNA fragmentation. TPA-induced differentiation of U-937 cells protects them from apoptosis induced by various agents (TNF, VBL). In contrast to U-937 cells, which require only 30 min of incubation with IFN for realization of its proapoptotic activity, increase of TFN cytotoxicity in K-562 and HEp-2 cells demands continuous presence of IFN in the medium. Such a phenomenon could provide the grounds for further analysis of IFN proapoptotic activity in vivo. Key Words: apoptosis, cell lines, cytotoxic effect, interferon, malignant tumors, tumor necrosis factor. Ïîêàçàíî, ùî ³íòåðôåðîí-àëüôà (²ÔÍ) ïîñèëþº öèòîòîêñè÷íó ä³þ ïðîòèïóõëèííèõ àãåíò³â, çîêðåìà ôàêòîðà íåêðîçó ïóõëèí (ÔÍÏ) òà â³íáëàñòèíó (ÂÁË), íà êë³òèíè ð³çíèõ ïóõëèííèõ ë³í³é in vitro (U-937, K-562, HEp-2 òà ³í.). îñíîâ³ öüîãî åôåêòó ëåaeèòü çäàòí³ñòü ²ÔÍ ïîñèëþâàòè àïîïòîç: â éîãî ïðèñóòíîñò³ äîñòîâ³ðíî çðîñòຠê³ëüê³ñòü àïîïòè÷íèõ êë³òèí òà ïîñèëþºòüñÿ îë³ãîíóêëåîñîìàëüíà ôðàãìåíòàö³ÿ ÿäåðíî¿ ÄÍÊ. ²íäóê-ö³ÿ äèôåðåíö³þâàííÿ ëåéêîçíèõ êë³òèí U-937 çà äîïîìîãîþ TPA çàõèùຠ¿õ â³ä àïîïòîçó, ³íäóêîâàíîãî ð³çíè-ìè ÷èííèêàìè (ÔÍÏ òà ÂÁË). Íà â³äì³íó â³ä êë³òèí ë³í³¿ U-937, ó ðàç³ êîíòàêòó ÿêèõ ç ²ÔÍ äîñòàòíüî 30 õâ äëÿ ïðîÿâó éîãî ïðîàïîïòè÷íî¿ ä³¿, â êë³òèíàõ ë³í³é K-562 òà HEp-2 äëÿ ï³äâèùåííÿ öèòîòîêñè÷íîñò³ ÔÍÏ íåîáõ³äíà ïîñò³éíà ïðèñóòí³ñòü ²ÔÍ. Öåé ôåíîìåí ðîçêðèâຠíîâó ãðàíü ó ìåõàí³çì³ ïðîòèïóõëèííî¿ ä³¿ ²ÔÍ ³ º ï³äñòàâîþ äëÿ äîñë³äaeåííÿ ïðîàïîïòè÷íî¿ ä³¿ ²ÔÍ â óìîâàõ in vivo. Êëþ÷îâ³ ñëîâà: àïîïòîç, â³íáëàñòèí, çëîÿê³ñí³ ïóõëèíè, êë³òèíí³ ë³í³¿, ³íòåðôåðîí, ôàêòîð íåêðîçó ïóõëèí, öèòîòîêñè÷íà ä³ÿ. Âèêîðèñòàí³ ñêîðî÷åííÿ: ÂÁË – â³íáëàñòèí; ²ÔÍ – ³íòåðôåðîí(è), ÔÍÏ — ôàêòîð íåêðîçó ïóõëèí; ÕÌË — õðîí³÷íèé 쳺ëîëåéêîç; ÖÒÄ – öèòîòîêñè÷íà ä³ÿ; PKR – äëÐÍÊ-èíäóêîâàíà ïðîòå¿íê³íàçà p68, TPA – òåòðàäåêàíî¿ë ôîðáîëì³ðèñòèëàò 13-àöåòàò. çëîÿê³ñí³é ïóõëèí³ òàê çâàíî¿ ïðîãðàìîâàíî¿ êë³òèí-íî¿ ñìåðò³, àáî àïîïòîçó, ÿêèé º ô³ç³îëîã³÷íèì ïðî-öåñîì, ñïðÿìîâàíèì íà çíèùåííÿ íåïîòð³áíèõ àáî øê³äëèâèõ äëÿ îðãàí³çìó êë³òèí, â òîìó ÷èñë³ ïóõ-ëèííèõ [20]. Îñòàíí³ì ÷àñîì áóëè îòðèìàí³ äàí³, ùî ñàìå àïîïòîç ëåaeèòü â îñíîâ³ ñòðèìóâàííÿ ðîñòó ì³êðîìåòàñòàç³â çà íàÿâíîñò³ îíêîëîã³÷íîãî ïðîöåñó [16, 27] ³ ñàìå öÿ ôîðìà çàãèáåë³ õàðàêòåðíà äëÿ ïóõëèííèõ êë³òèí ï³ä ÷àñ õ³ì³îòåðàﳿ [20]. Òîìó ïî-øóê ïðåïàðàò³â, çäàòíèõ ïîñèëþâàòè àïîïòè÷íó ä³þ ïðîòèïóõëèííèõ çàñîá³â àáî ïðèðîäíèõ öèòîòîêñè÷-íèõ ôàêòîð³â, º àêòóàëüíîþ ïðîáëåìîþ îíêîëî㳿. Ëîã³÷íî ïðèïóñòèòè, ùî ²ÔÍ, ÿê öèòîê³í ç øèðî-êèì ñïåêòðîì ðåãóëÿòîðíèõ ôóíêö³é, ìîaeå âèñòóïà-òè ³ ÿê ³íäóêòîð ÷è ìîäèô³êàòîð àïîïòîçó [4]. Äåÿê³ äàí³ ñâ³ä÷àòü, ùî ²ÔÍ, ñòèìóëþþ÷è ÷è ïðèãí³÷óþ÷è àïîïòîç ³ìóíîêîìïåòåíòíèõ êë³òèí, âêëþ÷àþ÷è Ò-êë³òèíè, ìàêðîôàãè òà åîçèíîô³ëüí³ ãðàíóëîöèòè, ìîaeå âèêîíóâàòè ôóíêö³þ ðåãóëÿòîðà àêòèâíîñò³ ³ìóííî¿ ñèñòåìè [5, 13, 22]. ßê ïðÿìèé ³íäóêòîð àïî-ïòîçó ïóõëèííèõ êë³òèí ²ÔÍ ä³º ëèøå â îêðåìèõ âè-ïàäêàõ. Çîêðåìà, â³í ìîaeå ³íäóêóâàòè àïîïòîç ó